The ability to fine-tune the production of proteins in a cell is essential for organisms to exist. An imbalance in protein levels can be the cause of various diseases. Messenger RNA molecules (mRNA) link the genetic information encoded in DNA and the produced proteins. Exactly how much protein is made mostly depends on the amount of mRNA in the cell’s cytoplasm. This is controlled by two processes: the synthesis of mRNA (also known as transcription) and mRNA being actively degraded.

Although much is known about mechanisms regulating transcription and degradation, how cells detect if they need to degrade mRNA based on the levels of its synthesis and vice versa is poorly understood. In 2013, researchers found that proteins known as 'RNA decay factors' responsible for mRNA degradation are actively moved from the cell’s cytoplasm into its nucleus to instruct the transcription machinery to produce more mRNA.

Kelbert, Jordán-Pla, de-Miguel-Jiménez et al. – including some of the researchers involved in the 2013 work – investigated how mRNA synthesis and degradation are coordinated to ensure a proper mRNA level. The researchers used advanced genome engineering methods to carefully manipulate and measure mRNA production and degradation in yeast cells.

The experiments revealed that the protein Sfp1 – a well-characterized transcription factor for stimulating the synthesis of a specific class of mRNAs inside the nucleus – can also prevent the degradation of these mRNAs outside the nucleus. During transcription, Sfp1 bound directly to mRNA. The investigators could manipulate the co-transcriptional binding of Sfp1 to a certain mRNA, thereby changing the mRNA stability in the cytoplasm.

This suggests that the ability of Sfp1 to regulate both the production and decay of mRNA is dependent on one another and that transcription can influence the fate of its transcripts. This combined activity can rapidly change mRNA levels in response to changes in the cell’s environment.

RNA plays a key role in ensuring correct levels of proteins. It can also function as an RNA molecule, independently of its coding capacity. Many cancers and developmental disorders are known to be caused by faulty interactions between transcription factors and nucleic acids. The finding that some transcription factors can directly regulate both mRNA synthesis and its destruction introduces new angles for studying and understanding these diseases.

In the last decade, investigators have accumulated evidence for a direct cross-talk between the transcriptional and post-transcriptional stages of gene expression. The dialogue between transcription and mRNA decay has been reported by several investigators, including us (Begley et al., 2019; Blasco-Moreno et al., 2019; Bregman et al., 2011; Bryll and Peterson, 2023; Buratti and Baralle, 2012; Chattopadhyay et al., 2022; El-Brolosy et al., 2019; Gilbertson et al., 2018; Goler-Baron et al., 2008; Haimovich et al., 2013b; Harel-Sharvit et al., 2010; Hartenian and Glaunsinger, 2019; Ma et al., 2019; Sun et al., 2012; Timmers and Tora, 2018; Trcek et al., 2011; Vera et al., 2014; Zid and O’Shea, 2014). Often, this dialog results in ‘mRNA buffering,’ which maintains an approximately constant mRNA level despite transient changes in mRNA synthesis or decay rates (Haimovich et al., 2013b; Sun et al., 2012). In particular, communication pathways have been discovered between promoters and mRNA translation (Chen et al., 2022; Vera et al., 2014; Zid and O’Shea, 2014) or decay (Bregman et al., 2011; Trcek et al., 2011). However, the underlying mechanism remains elusive.

During transcription by Pol II, several RNA-binding proteins (RBPs) bind to nascent transcripts, thus modulating the transcription cycle (Battaglia et al., 2017). Importantly, in some cases, RBPs remain bound to the mRNA, accompanying it to the cytoplasm and regulating post-transcriptional stages. For example, the Pol II subunits Rpb4 and Rpb7 bind to mRNAs and regulate their translation and decay (Goler-Baron et al., 2008; Harel-Sharvit et al., 2010). We named the latter cases ‘mRNA imprinting,’ because this binding imprints the mRNA fate (Choder, 2011; Dahan and Choder, 2013). Although Rpb4 is a quintessential imprinted factor, it functions as a general factor that binds to numerous mRNAs (Garrido-Godino et al., 2021). Imprinting by a ‘classical’ transcription factor (TF) that binds to specific promoters, thus regulating transcription by modulating the assembly of general transcription factors, including Pol II, is currently unknown. Such imprinting might broaden our understanding of the functions of TFs – not just transcription regulators but regulators of both the nuclear transcription and cytoplasmic post-transcription stages of gene expression.

We previously reported a special case of cross-talk between promoter elements and mRNA decay which is mediated by Rap1 binding sites (RapBSs) and by Rap1 protein (Bregman et al., 2011). RapBSs (12–14 bp) are found in ~5% of the promoters, including ~90% of ribosomal protein (RP) and a small portion of Ribosome Biogenesis (RiBi) promoters (Lascaris et al., 1999; Lieb et al., 2001; Shore et al., 2021; Warner, 1999). Rap1 is bound to essentially all such RP promoters in vivo (Lieb et al., 2001; Schawalder et al., 2004) and is involved in their transcription activation. Rap1 functions as a pioneering transcription factor (TF) required for the binding of a pair of RP-specific TFs called Fhl1 and Ifh1 (Lieb et al., 2001; Shore et al., 2021). An additional TF recruited by Rap1 is Sfp1 (see next paragraph). Previously, we demonstrated that Rap1 plays a dual role in maintaining the level of specific mRNAs – stimulating both mRNA synthesis and decay. We proposed that Rap1 represents a class of factors, synthegradases, whose recruitment to promoters stimulates (or represses) both mRNA synthesis and decay (Bregman et al., 2011). How Rap1 stimulates mRNA decay is unknown.

The split-finger protein 1 (Sfp1) is a zinc-finger TF, the deletion or overexpression of which has been shown to affect the recruitment of the TATA-binding protein (TBP) and Pol II to RiBi and RiBi-like genes, and to affect the transcription of RP and snoRNA genes (Albert et al., 2019; Jorgensen et al., 2004; Marion et al., 2004; Fingerman et al., 2003). It also impacts many G1/S (‘START’) genes, where it appears to act as a repressor (Albert et al., 2019). Sfp1 was, therefore, viewed as a classical TF. Shore’s lab has examined the Sfp1 configuration within promoters, using either chromatin immunoprecipitation (ChIP-seq) or chromatin endogenous cleavage (ChEC-seq), and found that the two approaches exhibit different sensitivity to different configurations. While Sfp1 binding sites detected by ChEC are enriched for the motif gAAAATTTTc, binding identified by ChIP is dependent on Ifh1, hence on Rap1 as well (Albert et al., 2019). Thus, Sfp1 can be viewed as a ‘classical’ zinc-finger containing TF. Zinc-finger domains have also been described to function as RNA-binding domains (Font and MacKay, 2010). In some proteins, such as TFIIIA, the same zinc-finger domain can recognize both a specific double-stranded DNA sequence and another specific sequence in single-stranded RNA - discussed in Font and MacKay, 2010.

In response to the misincorporation of nucleotides, damage to the DNA, nucleosomes, hairpins or certain DNA sequences, elongating Pol II transiently pauses. During pausing, Pol II remains catalytically active and can resume transcription if the obstacle is removed (Bar-Nahum et al., 2005; Gómez-Herreros et al., 2012a). However, these pauses increase the probability of Pol II backward movement along the DNA template, a process named ‘backtracking.’ During backtracking, the 3’ end of the nascent RNA extrudes from the active site, traps the trigger loop of the enzyme, and stably blocks mRNA elongation (Cheung and Cramer, 2011). Once arrested, Pol II can reactivate itself by cleaving its own synthetized RNA at the active site (Sigurdsson et al., 2010). Cleavage is substantially enhanced by TFIIS (Churchman and Weissman, 2011), which becomes essential under NTP scarcity (Archambault et al., 1992). Important for this paper, Pol II backtracking is highly frequent at RP and RiBi genes, compared to other gene regulons, and is highly dependent on Rap1 (Pelechano et al., 2009). Our previous work has also shown that several RP regulators, including Rap1 and Sfp1, make transcription of RP genes highly dependent on TFIIS, especially under conditions of transcriptional stress due to NTP depletion (Gómez-Herreros et al., 2012b). Thus, Sfp1 can be considered as a backtracking regulator. Regulators that antagonize Pol II backtracking are Xrn1 (Begley et al., 2021; Begley et al., 2019; Fischer et al., 2020), Rpb4 (Fischer et al., 2020) and the-Ccr4-Not complex (Collart, 2016), which prevents backtracking in a manner that depends on its Rpb4 and Rpb7 subunits (Babbarwal et al., 2014; Kruk et al., 2011). Interestingly, backtracking and TFIIS recruitment in RP genes are not influenced by Xrn1, but are strongly affected by Ccr4 (Begley et al., 2019).

Here, we assigned a much broader function to a TF in gene expression. We discovered that Sfp1 regulates both transcription and mRNA decay through its capacity to bind RNAs co-transcriptionally. The Sfp1-mediated cross-talk between mRNA synthesis and decay results in the cooperation of these opposing processes to increase mRNA abundance, by stimulating the former and repressing the latter. This cooperation is limited to a subgroup of Sfp1 targets, most of which are also Rap1 targets. Our results also unveil a role for some promoters as mediators between RPB and its interacting RNAs.

Sfp1 has traditionally been regarded as a ‘classical’ TF known to bind specific promoters, either through interactions with other TFs or by directly binding to promoter DNA (Albert et al., 2019; Reja et al., 2015). Further analysis that we performed using published ChIP-exo and ChEC-seq data has revealed an additional aspect of Sfp1’s binding behavior—it also interacts with gene bodies. Notably, the binding of Sfp1 to CRAC + gene bodies correlates with the presence of transcriptionally active Pol II molecules (Figure 5B), suggesting a physical association between Sfp1 and Pol II. Consequently, the binding of Sfp1 has an impact on Pol II configuration, stoichiometry, and backtracking, particularly in the context of CRAC + genes (Figures 6 and 7). This alteration in the Pol II configuration is reflected in the increased backtracking frequency, as indicated by the BI values. Moreover, the binding of Sfp1 to gene bodies correlates with Pol II activity, particularly within CRAC + genes (Figure 5B). Thus, Sfp1’s function in a subset of its target genes extends beyond transcription initiation and encompasses transcription elongation, as we proposed earlier (Gómez-Herreros et al., 2012b). Based on the following observations, we propose that Sfp1 binds to Pol II in proximity to both DNA and Rpb4, accompanying Pol II during elongation and influencing its configuration, thereby enhancing its propensity to backtrack (Figure 8A): (I) Sfp1 physically interacts with Rpb4, either directly or indirectly (Figure 1—figure supplement 1). (II) ChIP-exo results, dependent on Sfp1’s cross-linking with DNA, indicate Sfp1’s presence near DNA, both at promoters and gene bodies (Figure 5A). (III) Sfp1 influences Pol II configuration in a manner that impacts the architecture or stoichiometry of Rpb4 within Pol II (Figure 7). (IV) Sfp1 binding to chromatin better correlates with all Pol II (both backtracked and active) than with transcriptionally active Pol II, examined by BioGRO-seq (Figure 5B). (V) The global reduction in BI is observed upon the deletion of SFP1 (Figures 6 and 7).

Figure 8

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The effects of Sfp1 on backtracking occur in the context of Rpb4 (Figure 7B). We note that backtracking is influenced by the alteration of Rpb4 within the elongation complex, independently of Sfp1, as the correlation between Rpb4 ChIP/Rpb3 ChIP ratios and BI is still present, albeit more mildly, in sfp1∆. Rpb4/7 was previously implicated in backtracking either by itself (Fischer et al., 2020) or in the context of the Ccr4-NOT complex (Babbarwal et al., 2014; Kruk et al., 2011). It is possible that the effect of Sfp1 on backtracking is through changing Rpb4 stoichiometry within Pol II or Rpb4 conformation. Backtracking is a conserved process across evolution that influences Pol II processivity and transcription rate (Bar-Nahum et al., 2005). We propose an additional potential function: the backtracking-prone configuration of Pol II might be more compatible with mRNA imprinting than the ‘regular’ configuration (Figure 8A). This hypothesis is inspired by the following observations: (I) Sfp1 shows a positive general influence on mRNA stability that is maximal in those mRNAs that it physically binds (Figure 4A ‘HL,’ 4B, and 6 C). (II) Sfp1 physical interaction with mRNAs occurs cotranscriptional (Figure 5C and Figure 2—figure supplement 1D). (III) The stronger the effect of Sfp1 on Pol II backtracking the stronger its effect on mRNA HL (Figure 6D). (IV) Backtracking is substantially more frequent in those genes whose mRNAs are bound by Sfp1 compared to the genome average, and significantly more dependent on this factor (Figure 6B and C). Taking all these observations together, it appears that backtracking is associated with co-transcriptional binding of Sfp1 to nascent RNA. Reassuringly, RiBi genes that exhibit Sfp1-dependent backtracking also imprint Sfp1, whereas those that do not also do not imprint (Figure 6B, ‘RiBi CRAC+,’ and ‘RiBi non-CRAC+’).

Unexpectedly, in addition to its chromatin binding feature, we find that Sfp1 binds a subpopulation of mRNAs whose transcription is stimulated by Sfp1 – ‘CRAC +mRNAs.’ CRAC + mRNAs exhibit distinctive characteristics compared to other Sfp1-regulated genes (whose mRNAs do not bind Sfp1), or other non-Sfp1-regulated genes (Figures 2A-C—7A-B, Figure 2—figure supplement 1D, F, Figure 4—figure supplement 2A-B, Figure 7—figure supplement 1A-B). Collectively, these findings demonstrate that CRAC + genes and their transcripts constitute a unique group, distinguishable from others based on several criteria, only one of them is the ability of their transcripts to bind Sfp1. CRAC + genes display a broad range of transcription rates (Figure 6A) and behave differently from the most highly transcribed genes (Figure 7A). Furthermore, while all RiBi mRNAs exhibit similar expression levels, only a subset of them binds to Sfp1. These observations collectively suggest that the 262 CRAC + constitute a distinct set of genes that unveils a new paradigm: genes controlled by a common factor both transcriptionally and post-transcriptionally, via mRNA imprinting.

We observed that RapBS-mediated promoter binding is critical for Sfp1 capacity to bind RNA (Figure 3). In RiBi genes, we found highly significant correspondence between the propensity of RiBi promoters to carry RapBS and binding of RiBi mRNAs to Sfp1 (Figure 3C). We propose that RNA-binding occurs co-transcriptionally for the following reasons: (I) Sfp1 export from the nucleus to the cytoplasm is dependent on transcription (Figure 1A), suggesting that it is exported together with the Pol II transcripts. (II) Splicing occurs co-transcriptionally (e.g. Churchman and Weissman, 2011). Consistent with co-transcriptional binding, Sfp1 binds intron-containing RPL30 RNA (Figure 2D; note that the ratio between intron-containing RNA and mature RNA is higher in the IPed lane than in the input one). (III) Binding of Sfp1 to mRNA is dependent on RapBS, suggesting that the same Sfp1 recruited to the promoter by Rap1 binds the transcript. (IV) The ChIP-exo signal drops past the GCTGCT motif in C1-C2 genes (for clusters’ definition see Figure 2B), a position where Sfp1 prefers to bind the motif containing CRAC + transcripts (Figure 5C). These observations suggest that, at least in some of their mRNA targets, Sfp1 is released from Rpb4-containing Pol II to the nascent transcripts co-transcriptionally as GCTGCT motif emerges from Pol II. However, many CRAC + do not contain detectable GCTGCT motifs or have it in a different position (Figure 2BC3 cluster). Our observation that RapBS is required to promote binding to the RPL30 mRNA sequence, a gene that contains the motif, (Figure 3B) demonstrates that motif 1 is not sufficient to recruit Sfp1. Perhaps this motif is used to stabilize the interaction. In the absence of the motif, the movement from Rpb4-containing Pol II to the emerging transcript might be related to the process of polyadenylation (see Figure 2A). Collectively, our results unveil a role for CRAC + promoters as mediators between RPB and its interacting RNAs. Whether Rpb4 dissociates together with these proteins remains to be determined. Whether the probability of mRNA imprinting is affected by the time Pol II is engaged in backtracking, until its resolution by TFIIS, is another appealing hypothesis that remains to be examined.

Binding of Sfp1 to mRNAs regulates deadenylation-mediated mRNA decay, mainly by slowing down these processes (Figure 4). Following mRNA decay, Sfp1 is imported back to the nucleus (Figure 1—figure supplement 1B, C). Following the import, Sfp1 binds to specific promoters and regulates transcription, closing the circle of gene expression regulation (Figure 8B). In this way, the synthesis and decay of Sfp1-regulated mRNAs are coordinated in a manner that maintains proper mRNA levels of a specific subset of genes.

The capacity of Sfp1 to bind mature mRNA adds additional complexity to the expression of CRAC + genes. Here, we report that Sfp1 regulates the levels of these gene products by two mechanisms: by stimulation of synthesis and by repression of decay. This raises a possible new mode of regulating mRNA level that targets the Sfp1 imprinting machinery, the extent of which would determine the mRNA HL and consequently the mRNA level. Since Sfp1 enhances both mRNA synthesis and stability, it can serve as a signaling pathway target to rapidly regulate the expression of its clients. Indeed, the expression of Sfp1 targets is highly responsive to the environment (Albert et al., 2019; Jorgensen et al., 2004).

Sfp1 was viewed as a classical TF that specifically modulates the transcription of a subset of a few hundred genes (see Introduction). We were, therefore, surprised to discover a genome-wide effects of Sfp1 depletion or deletion (Figures 4B, 6A, D, 7B–C). These results, in combination with the weak interaction of Sfp1 with chromatin (Figure 5A ‘Sfp1 Control’), are in accord with previous observation that expression of >30% of the genes, most are not considered to be direct targets of Sfp1, is affected by either Sfp1 depletion or its overexpression (Albert et al., 2019, and our unpublished NET-seq data). An important support for this notion is the correlation we found between the binding of Sfp1 to gene bodies and Pol II occupancy in all genes (Figure 5B). The general capacity of Sfp1 to alter elongating Pol II in the context of Rpb4 and to affect backtracking (Figure 7B, Figure 7—figure supplement 1A) likely underlies its widespread effect on transcription.

As mentioned above, this widespread effect of Sfp1 on backtracking correlates with higher mRNA HL in many genes (not only in CRAC+; Figure 6D). This suggests that the effect of Sfp1-dependent backtracking on mRNA HL does not always require Sfp1 binding to mRNA. Perhaps, this indirect effect of Sfp1 on mRNA HL is mediated by other factors, like Ccr4-Not, whose imprinting may also be affected by Pol II backtracking (Kruk et al., 2011; Villanyi et al., 2014; Begley et al., 2019). In contrast, the correlation between Rpb4/Rpb3 and mRNA HL is much higher in CRAC + than in the rest of the genome, and is entirely dependent on Sfp1 (Figure 7C, Figure 7—figure supplement 1B). Interestingly, we previously demonstrated that transcription elongation of Rap1-controlled genes is exceptionally affected by backtracking (Pelechano et al., 2009). We propose that Rap1-dependent recruitment of Sfp1 modulates its interaction with Pol II in a manner that permits Sfp1 transfer to mRNA (Figure 8).

Binding of Sfp1 to CRAC + mRNAs, which stabilizes the bound mRNAs, is dependent on Rap1 binding sites. On the other hand, we previously found that depletion of Rap1 leads to mRNA stabilization (Bregman et al., 2011). If the effect of Rap1 on mRNA stability is mediated only through Sfp1, we would expect that its depletion should result in mRNA destabilization, contrary to our previous observation (Bregman et al., 2011). Therefore, we conclude that Rap1 mediates additional activity that enhances mRNA decay and overrides the destabilizing effect of Sfp1, which remains to be discovered.

The Rpb4 stoichiometry within yeast Pol II is <1 (Choder and Young, 1993). It was not clear whether the sub-stoichiometric feature of Rpb4 is constant across all Pol II molecules. Here, we show that stoichiometry, as reflected by the Rpb4 ChIP/Rpb3 ChIP ratio, decreases gradually during transcription elongation. It is possible that there is a link between the Rpb4 capacity to modulate backtracking and the gradual decrease in its stoichiometry. Interestingly Sfp1 affects this stoichiometry drop, thus serving as a regulator of Rpb4 stoichiometry. Moreover, the effect of Sfp1 on mRNA stability is entirely linked to its action on Rpb4 stoichiometry (Figure 7C and Figure 7—figure supplement 1B). We note, however, that, although changes in the stoichiometry are the most likely interpretation of the change in Rpb4 ChIP/Rpb3 ChIP ratio, this change can merely reflect changes in Pol II configuration that compromise the capacity of Rpb4 to produce ChIP signal.

Interestingly, the Sfp1-mediated mechanism contrasts with that of mRNA buffering. The known model of mRNA buffering posits that a modulation of one process (e.g. transcription) is balanced by a reciprocal modulation of the other process (e.g. mRNA decay), thus maintaining the mRNA level constant, or nearly constant (Bryll and Peterson, 2023; Haimovich et al., 2013b; Pérez-Ortín and Chávez, 2022; Timmers and Tora, 2018). In contrast, the functions of Sfp1 do not result in balancing, but the contrary: the two activities of Sfp1 cooperatively increase mRNA level – increase mRNA synthesis and decrease its degradation. Thus, Sfp1 is a paramount example of enhanced gene regulation by cooperation between mRNA decay and gene transcription that we previously modeled (García-Martínez et al., 2023). Moreover, we reported that mRNA buffering maintains a constant mRNA concentration regardless of the strain growth rate, except for growth-related genes (García-Martínez et al., 2016; Chattopadhyay et al., 2022; Pérez-Ortín and Chávez, 2022). The expression of the latter genes increases with growth rate. The discovered effect of Sfp1 on its target genes, most of which are growth-related, provides a plausible mechanism to explain how growth-related genes avoid buffering when their expression must be rapidly adjusted to the ever-changing environment.

In summary, we propose that the role of certain class-specific TFs, such as Sfp1, extends beyond merely controlling various stages of mRNA synthesis and processing in the nucleus; they also regulate post-transcriptional functions in the cytoplasm. We hypothesize that a single factor (or a complex of factors) has evolved the capacity to regulate both transcriptional and post-transcriptional functions to facilitate cross-talk between these two mechanisms. Sfp1 impacts the mRNA life cycle - from transcription to degradation. Interestingly, the Sfp1 effect on transcription elongation is linked to its function on mRNA stabilization, suggesting that all its functions are connected. Sfp1 possesses two classical zinc fingers. Given that proteins with zinc fingers, characteristic of many TFs, are known to be involved in DNA, RNA, and protein binding, it is conceivable that this zinc finger-containing protein is suitable for participating in the mRNA imprinting process, as proposed here (Figure 8B). Given that RBPs have been proposed to perform multiple roles in RNA-based regulation of gene expression in mammals (Xiao et al., 2019), we anticipate that the case of Sfp1 as an imprinting factor will serve an example of this important type of gene regulators in other eukaryotes.

All data generated or analysed during this study are included in the manuscript and supporting files.

1. 1. Pérez-Ortín JE
   2. García-Martínez J

   (2023) NCBI Gene Expression Omnibus

   ID GSE202748. Transcriptomic analysis of the effect of Sfp1 depletion.

   https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202748
2. 1. Kelbert M
   2. Choder M
   3. Pérez-Ortín JE
   4. Chávez S
   5. Jordán-Pla A
   6. Granneman S

   (2023) NCBI Gene Expression Omnibus

   ID GSE230761. The transcription factor Sfp1 imprints specific classes of mRNAs and links their synthesis and cytoplasmic decay.

   https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE230761

1. 1. García-Martínez J
   2. Pérez-Ortín JE
   3. Medina DA
   4. Choder M
   5. Chávez S

   (2015) NCBI Gene Expression Omnibus

   ID GSE57467. Genomic Run On (GRO): determination of the nascent transcriptional rates and mRNA levels in several yeast mutants.

   https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57467

1. 1. Albert B
   2. Tomassetti S
   3. Gloor Y
   4. Dilg D
   5. Mattarocci S
   6. Kubik S
   7. Hafner L
   8. Shore D

   (2019) Sfp1 regulates transcriptional networks driving cell growth and division through multiple promoter-binding modes

   Genes & Development 33:288–293.

   https://doi.org/10.1101/gad.322040.118

   • PubMed
   • Google Scholar
2. 1. Archambault J
   2. Lacroute F
   3. Ruet A
   4. Friesen JD

   (1992) Genetic interaction between transcription elongation factor TFIIS and RNA polymerase II

   Molecular and Cellular Biology 12:4142–4152.

   https://doi.org/10.1128/mcb.12.9.4142-4152.1992

   • PubMed
   • Google Scholar
3. 1. Babbarwal V
   2. Fu J
   3. Reese JC

   (2014) The Rpb4/7 module of RNA polymerase II is required for carbon catabolite repressor protein 4-negative on TATA (Ccr4-not) complex to promote elongation

   The Journal of Biological Chemistry 289:33125–33130.

   https://doi.org/10.1074/jbc.C114.601088

   • PubMed
   • Google Scholar
4. 1. Bar-Nahum G
   2. Epshtein V
   3. Ruckenstein AE
   4. Rafikov R
   5. Mustaev A
   6. Nudler E

   (2005) A ratchet mechanism of transcription elongation and its control

   Cell 120:183–193.

   https://doi.org/10.1016/j.cell.2004.11.045

   • PubMed
   • Google Scholar
5. 1. Battaglia S
   2. Lidschreiber M
   3. Baejen C
   4. Torkler P
   5. Vos SM
   6. Cramer P

   (2017) RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases

   eLife 6:e25637.

   https://doi.org/10.7554/eLife.25637

   • PubMed
   • Google Scholar
6. 1. Begley V
   2. Corzo D
   3. Jordán-Pla A
   4. Cuevas-Bermúdez A
   5. Miguel-Jiménez L
   6. de Pérez-Aguado D
   7. Machuca-Ostos M
   8. Navarro F
   9. Chávez MJ
   10. Pérez-Ortín JE
   11. Chávez S

   (2019) The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4

   Nucleic Acids Research 47:9524–9541.

   https://doi.org/10.1093/nar/gkz660

   • PubMed
   • Google Scholar
7. 1. Begley V
   2. Jordán-Pla A
   3. Peñate X
   4. Garrido-Godino AI
   5. Challal D
   6. Cuevas-Bermúdez A
   7. Mitjavila A
   8. Barucco M
   9. Gutiérrez G
   10. Singh A
   11. Alepuz P
   12. Navarro F
   13. Libri D
   14. Pérez-Ortín JE
   15. Chávez S

   (2021) Xrn1 influence on gene transcription results from the combination of general effects on elongating RNA pol II and gene-specific chromatin configuration

   RNA Biology 18:1310–1323.

   https://doi.org/10.1080/15476286.2020.1845504

   • PubMed
   • Google Scholar
8. 1. Blasco-Moreno B
   2. de Campos-Mata L
   3. Böttcher R
   4. García-Martínez J
   5. Jungfleisch J
   6. Nedialkova DD
   7. Chattopadhyay S
   8. Gas ME
   9. Oliva B
   10. Pérez-Ortín JE
   11. Leidel SA
   12. Choder M
   13. Díez J

   (2019) The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins

   Nature Communications 10:1298.

   https://doi.org/10.1038/s41467-019-09199-6

   • PubMed
   • Google Scholar
9. 1. Bohnsack MT
   2. Tollervey D
   3. Granneman S

   (2012) Identification of RNA Helicase Target Sites by UV Cross-Linking and Analysis of cDNA

   Methods in Enzymology 1:275–288.

   https://doi.org/10.1016/B978-0-12-396546-2.00013-9

   • Google Scholar
10. 1. Bregman A
    2. Avraham-Kelbert M
    3. Barkai O
    4. Duek L
    5. Guterman A
    6. Choder M

    (2011) Promoter elements regulate cytoplasmic mRNA decay

    Cell 147:1473–1483.

    https://doi.org/10.1016/j.cell.2011.12.005

    • PubMed
    • Google Scholar
11. 1. Bresson S
    2. Shchepachev V
    3. Spanos C
    4. Turowski TW
    5. Rappsilber J
    6. Tollervey D

    (2020) Stress-induced translation inhibition through rapid displacement of scanning initiation factors

    Molecular Cell 80:470–484.

    https://doi.org/10.1016/j.molcel.2020.09.021

    • PubMed
    • Google Scholar
12. 1. Bryll AR
    2. Peterson CL

    (2023) The circular logic of mRNA homeostasis

    Transcription 14:18–26.

    https://doi.org/10.1080/21541264.2023.2183684

    • PubMed
    • Google Scholar
13. 1. Buratti E
    2. Baralle FE

    (2012) TDP-43: gumming up neurons through protein-protein and protein-RNA interactions

    Trends in Biochemical Sciences 37:237–247.

    https://doi.org/10.1016/j.tibs.2012.03.003

    • PubMed
    • Google Scholar
14. 1. Chattopadhyay S
    2. Garcia-Martinez J
    3. Haimovich G
    4. Khwaja A
    5. Barkai O
    6. Ghosh A
    7. Chuarzman SG
    8. Schuldiner M
    9. Elran R
    10. Rosenberg M
    11. Bohnsack K
    12. Bohnsack M
    13. Perez-Ortin JE
    14. Choder M

    (2022) RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and initiates a novel mRNA decay pathway

    Nature Communications 13:7184–7201.

    https://doi.org/10.1101/2021.04.01.437949

    • Google Scholar
15. 1. Chen YS
    2. Hou W
    3. Tracy S
    4. Harvey AT
    5. Harjono V
    6. Xu F
    7. Moresco JJ
    8. Yates JR
    9. Zid BM

    (2022) Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

    eLife 11:e76965.

    https://doi.org/10.7554/eLife.76965

    • PubMed
    • Google Scholar
16. 1. Cheung ACM
    2. Cramer P

    (2011) Structural basis of RNA polymerase II backtracking, arrest and reactivation

    Nature 471:249–253.

    https://doi.org/10.1038/nature09785

    • PubMed
    • Google Scholar
17. 1. Choder M
    2. Young RA

    (1993) A portion of RNA polymerase II molecules has A component essential for stress responses and stress survival

    Molecular and Cellular Biology 13:6984–6991.

    https://doi.org/10.1128/mcb.13.11.6984-6991.1993

    • PubMed
    • Google Scholar
18. 1. Choder M

    (2004) Rpb4 and Rpb7: subunits of RNA polymerase II and beyond

    Trends in Biochemical Sciences 29:674–681.

    https://doi.org/10.1016/j.tibs.2004.10.007

    • PubMed
    • Google Scholar
19. 1. Choder M

    (2011) mRNA imprinting

    Cellular Logistics 1:37–40.

    https://doi.org/10.4161/cl.1.1.14465

    • Google Scholar
20. 1. Churchman LS
    2. Weissman JS

    (2011) Nascent transcript sequencing visualizes transcription at nucleotide resolution

    Nature 469:368–373.

    https://doi.org/10.1038/nature09652

    • PubMed
    • Google Scholar
21. 1. Collart MA

    (2016) The Ccr4-Not complex is a key regulator of eukaryotic gene expression

    Wiley Interdisciplinary Reviews. RNA 7:438–454.

    https://doi.org/10.1002/wrna.1332

    • PubMed
    • Google Scholar
22. 1. Dahan N
    2. Choder M

    (2013) The eukaryotic transcriptional machinery regulates mRNA translation and decay in the cytoplasm

    Biochimica et Biophysica Acta 1829:169–173.

    https://doi.org/10.1016/j.bbagrm.2012.08.004

    • PubMed
    • Google Scholar
23. 1. Duek L
    2. Barkai O
    3. Elran R
    4. Adawi I
    5. Choder M

    (2018) Dissociation of Rpb4 from RNA polymerase II is important for yeast functionality

    PLOS ONE 13:e0206161.

    https://doi.org/10.1371/journal.pone.0206161

    • PubMed
    • Google Scholar
24. 1. El-Brolosy MA
    2. Kontarakis Z
    3. Rossi A
    4. Kuenne C
    5. Günther S
    6. Fukuda N
    7. Kikhi K
    8. Boezio GLM
    9. Takacs CM
    10. Lai SL
    11. Fukuda R
    12. Gerri C
    13. Giraldez AJ
    14. Stainier DYR

    (2019) Genetic compensation triggered by mutant mRNA degradation

    Nature 568:193–197.

    https://doi.org/10.1038/s41586-019-1064-z

    • PubMed
    • Google Scholar
25. 1. Farago M
    2. Nahari T
    3. Hammel C
    4. Cole CN
    5. Choder M

    (2003) Rpb4p, a subunit of RNA polymerase II, mediates mRNA export during stress

    Molecular Biology of the Cell 14:2744–2755.

    https://doi.org/10.1091/mbc.e02-11-0740

    • PubMed
    • Google Scholar
26. 1. Fingerman I
    2. Nagaraj V
    3. Norris D
    4. Vershon AK

    (2003) Sfp1 plays a key role in yeast ribosome biogenesis

    Eukaryotic Cell 2:1061–1068.

    https://doi.org/10.1128/EC.2.5.1061-1068.2003

    • PubMed
    • Google Scholar
27. 1. Fischer J
    2. Song YS
    3. Yosef N
    4. di Iulio J
    5. Churchman LS
    6. Choder M

    (2020) The yeast exoribonuclease Xrn1 and associated factors modulate RNA polymerase II processivity in 5’ and 3’ gene regions

    The Journal of Biological Chemistry 295:11435–11454.

    https://doi.org/10.1074/jbc.RA120.013426

    • PubMed
    • Google Scholar
28. 1. Font J
    2. MacKay JP

    (2010) Beyond DNA: Zinc finger domains as RNA-binding modules

    Methods in Molecular Biology 649:479–491.

    https://doi.org/10.1007/978-1-60761-753-2_29/FIGURES/2

    • Google Scholar
29. 1. García-Martínez J
    2. Aranda A
    3. Pérez-Ortín JE

    (2004) Genomic run-on evaluates transcription rates for all yeast genes and identifies gene regulatory mechanisms

    Molecular Cell 15:303–313.

    https://doi.org/10.1016/j.molcel.2004.06.004

    • PubMed
    • Google Scholar
30. 1. García-Martínez J
    2. Troulé K
    3. Chávez S
    4. Pérez-Ortín JE

    (2016) Growth rate controls mRNA turnover in steady and non-steady states

    RNA Biology 13:1175–1181.

    https://doi.org/10.1080/15476286.2016.1236171

    • PubMed
    • Google Scholar
31. 1. García-Martínez J
    2. Singh A
    3. Medina D
    4. Chávez S
    5. Pérez-Ortín JE

    (2023) Enhanced gene regulation by cooperation between mRNA decay and gene transcription

    Biochimica et Biophysica Acta. Gene Regulatory Mechanisms 1866:194910.

    https://doi.org/10.1016/j.bbagrm.2023.194910

    • PubMed
    • Google Scholar
32. 1. Garrido-Godino AI
    2. Gupta I
    3. Gutiérrez-Santiago F
    4. Martínez-Padilla AB
    5. Alekseenko A
    6. Steinmetz LM
    7. Pérez-Ortín JE
    8. Pelechano V
    9. Navarro F

    (2021) Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast

    RNA Biology 18:1206–1220.

    https://doi.org/10.1080/15476286.2020.1839229

    • PubMed
    • Google Scholar
33. 1. Gilbertson S
    2. Federspiel JD
    3. Hartenian E
    4. Cristea IM
    5. Glaunsinger B

    (2018) Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription

    eLife 7:e37663.

    https://doi.org/10.7554/eLife.37663

    • PubMed
    • Google Scholar
34. 1. Goler-Baron V
    2. Selitrennik M
    3. Barkai O
    4. Haimovich G
    5. Lotan R
    6. Choder M

    (2008) Transcription in the nucleus and mRNA decay in the cytoplasm are coupled processes

    Genes & Development 22:2022–2027.

    https://doi.org/10.1101/gad.473608

    • PubMed
    • Google Scholar
35. 1. Gómez-Herreros F
    2. de Miguel-Jiménez L
    3. Millán-Zambrano G
    4. Peñate X
    5. Delgado-Ramos L
    6. Muñoz-Centeno MC
    7. Chávez S

    (2012a) One step back before moving forward: regulation of transcription elongation by arrest and backtracking

    FEBS Letters 586:2820–2825.

    https://doi.org/10.1016/j.febslet.2012.07.030

    • PubMed
    • Google Scholar
36. 1. Gómez-Herreros F
    2. de Miguel-Jiménez L
    3. Morillo-Huesca M
    4. Delgado-Ramos L
    5. Muñoz-Centeno MC
    6. Chávez S

    (2012b) TFIIS is required for the balanced expression of the genes encoding ribosomal components under transcriptional stress

    Nucleic Acids Research 40:6508–6519.

    https://doi.org/10.1093/nar/gks340

    • PubMed
    • Google Scholar
37. 1. Granneman S
    2. Kudla G
    3. Petfalski E
    4. Tollervey D

    (2009) Identification of protein binding sites on U3 snoRNA and pre-rRNA by UV cross-linking and high-throughput analysis of cDNAs

    PNAS 106:9613–9618.

    https://doi.org/10.1073/pnas.0901997106

    • PubMed
    • Google Scholar
38. 1. Haag S
    2. Kretschmer J
    3. Sloan KE
    4. Bohnsack MT

    (2017) Crosslinking Methods to Identify RNA Methyltransferase Targets in vivo Methods

    Molecular Biology 1:269–281.

    https://doi.org/10.1007/978-1-4939-6807-7_18

    • Google Scholar
39. 1. Haimovich G
    2. Choder M
    3. Singer RH
    4. Trcek T

    (2013a) The fate of the messenger is pre-determined: A new model for regulation of gene expression

    Biochimica et Biophysica Acta 1829:643–653.

    https://doi.org/10.1016/j.bbagrm.2013.01.004

    • PubMed
    • Google Scholar
40. 1. Haimovich G
    2. Medina DA
    3. Causse SZ
    4. Garber M
    5. Millán-Zambrano G
    6. Barkai O
    7. Chávez S
    8. Pérez-Ortín JE
    9. Darzacq X
    10. Choder M

    (2013b) Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis

    Cell 153:1000–1011.

    https://doi.org/10.1016/j.cell.2013.05.012

    • PubMed
    • Google Scholar
41. 1. Harel-Sharvit L
    2. Eldad N
    3. Haimovich G
    4. Barkai O
    5. Duek L
    6. Choder M

    (2010) RNA polymerase II subunits link transcription and mRNA decay to translation

    Cell 143:552–563.

    https://doi.org/10.1016/j.cell.2010.10.033

    • PubMed
    • Google Scholar
42. 1. Hartenian E
    2. Glaunsinger BA

    (2019) Feedback to the central dogma: cytoplasmic mRNA decay and transcription are interdependent processes

    Critical Reviews in Biochemistry and Molecular Biology 54:385–398.

    https://doi.org/10.1080/10409238.2019.1679083

    • PubMed
    • Google Scholar
43. 1. Jordán-Pla A
    2. Gupta I
    3. de Miguel-Jiménez L
    4. Steinmetz LM
    5. Chávez S
    6. Pelechano V
    7. Pérez-Ortín JE

    (2015) Chromatin-dependent regulation of RNA polymerases II and III activity throughout the transcription cycle

    Nucleic Acids Research 43:787–802.

    https://doi.org/10.1093/nar/gku1349

    • PubMed
    • Google Scholar
44. 1. Jorgensen P
    2. Rupes I
    3. Sharom JR
    4. Schneper L
    5. Broach JR
    6. Tyers M

    (2004) A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size

    Genes & Development 18:2491–2505.

    https://doi.org/10.1101/gad.1228804

    • PubMed
    • Google Scholar
45. 1. Kruk JA
    2. Dutta A
    3. Fu J
    4. Gilmour DS
    5. Reese JC

    (2011) The multifunctional Ccr4-Not complex directly promotes transcription elongation

    Genes & Development 25:581–593.

    https://doi.org/10.1101/gad.2020911

    • PubMed
    • Google Scholar
46. 1. Lascaris RF
    2. Mager WH
    3. Planta RJ

    (1999) DNA-binding requirements of the yeast protein Rap1p as selected in silico from ribosomal protein gene promoter sequences

    Bioinformatics 15:267–277.

    https://doi.org/10.1093/bioinformatics/15.4.267

    • PubMed
    • Google Scholar
47. 1. Lee MS
    2. Henry M
    3. Silver PA

    (1996) A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export

    Genes & Development 10:1233–1246.

    https://doi.org/10.1101/gad.10.10.1233

    • Google Scholar
48. 1. Lieb JD
    2. Liu X
    3. Botstein D
    4. Brown PO

    (2001) Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association

    Nature Genetics 28:327–334.

    https://doi.org/10.1038/ng569

    • PubMed
    • Google Scholar
49. 1. Lotan R
    2. Bar-On VG
    3. Harel-Sharvit L
    4. Duek L
    5. Melamed D
    6. Choder M

    (2005) The RNA polymerase II subunit Rpb4p mediates decay of a specific class of mRNAs

    Genes & Development 19:3004–3016.

    https://doi.org/10.1101/gad.353205

    • PubMed
    • Google Scholar
50. 1. Lotan R
    2. Goler-Baron V
    3. Duek L
    4. Haimovich G
    5. Choder M

    (2007) The Rpb7p subunit of yeast RNA polymerase II plays roles in the two major cytoplasmic mRNA decay mechanisms

    The Journal of Cell Biology 178:1133–1143.

    https://doi.org/10.1083/jcb.200701165

    • PubMed
    • Google Scholar
51. 1. Luo Y
    2. Na Z
    3. Slavoff SA

    (2018) P-Bodies: Composition, properties, and functions

    Biochemistry 57:2424–2431.

    https://doi.org/10.1021/acs.biochem.7b01162

    • PubMed
    • Google Scholar
52. 1. Ma Z
    2. Zhu P
    3. Shi H
    4. Guo L
    5. Zhang Q
    6. Chen Y
    7. Chen S
    8. Zhang Z
    9. Peng J
    10. Chen J

    (2019) PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components

    Nature 568:259–263.

    https://doi.org/10.1038/s41586-019-1057-y

    • PubMed
    • Google Scholar
53. 1. Marion RM
    2. Regev A
    3. Segal E
    4. Barash Y
    5. Koller D
    6. Friedman N
    7. O’Shea EK

    (2004) Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression

    PNAS 101:14315–14322.

    https://doi.org/10.1073/pnas.0405353101

    • PubMed
    • Google Scholar
54. 1. Nishimura K
    2. Fukagawa T
    3. Takisawa H
    4. Kakimoto T
    5. Kanemaki M

    (2009) An auxin-based degron system for the rapid depletion of proteins in nonplant cells

    Nature Methods 6:917–922.

    https://doi.org/10.1038/nmeth.1401

    • PubMed
    • Google Scholar
55. 1. Oliete-Calvo P
    2. Serrano-Quílez J
    3. Nuño-Cabanes C
    4. Pérez-Martínez ME
    5. Soares LM
    6. Dichtl B
    7. Buratowski S
    8. Pérez-Ortín JE
    9. Rodríguez-Navarro S

    (2018) A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export

    EMBO Reports 19:e45992.

    https://doi.org/10.15252/embr.201845992

    • PubMed
    • Google Scholar
56. 1. Parker R

    (2012) RNA degradation in Saccharomyces cerevisae

    Genetics 191:671–702.

    https://doi.org/10.1534/genetics.111.137265

    • PubMed
    • Google Scholar
57. 1. Pelechano V
    2. Jimeno-González S
    3. Rodríguez-Gil A
    4. García-Martínez J
    5. Pérez-Ortín JE
    6. Chávez S

    (2009) Regulon-specific control of transcription elongation across the yeast genome

    PLOS Genetics 5:e1000614.

    https://doi.org/10.1371/journal.pgen.1000614

    • PubMed
    • Google Scholar
58. 1. Pérez-Ortín JE
    2. Chávez S

    (2022) Nucleo-cytoplasmic shuttling of RNA-binding factors: mRNA buffering and beyond

    Biochimica et Biophysica Acta. Gene Regulatory Mechanisms 1865:194849.

    https://doi.org/10.1016/j.bbagrm.2022.194849

    • PubMed
    • Google Scholar
59. 1. Puig O
    2. Caspary F
    3. Rigaut G
    4. Rutz B
    5. Bouveret E
    6. Bragado-Nilsson E
    7. Wilm M
    8. Séraphin B

    (2001) The tandem affinity purification (TAP) method: a general procedure of protein complex purification

    Methods 24:218–229.

    https://doi.org/10.1006/meth.2001.1183

    • PubMed
    • Google Scholar
60. 1. Reja R
    2. Vinayachandran V
    3. Ghosh S
    4. Pugh BF

    (2015) Molecular mechanisms of ribosomal protein gene coregulation

    Genes & Development 29:1942–1954.

    https://doi.org/10.1101/gad.268896.115

    • PubMed
    • Google Scholar
61. 1. Rodríguez-Gil A
    2. García-Martínez J
    3. Pelechano V
    4. Muñoz-Centeno M de la C
    5. Geli V
    6. Pérez-Ortín JE
    7. Chávez S

    (2010) The distribution of active RNA polymerase II along the transcribed region is gene-specific and controlled by elongation factors

    Nucleic Acids Research 38:4651–4664.

    https://doi.org/10.1093/nar/gkq215

    • PubMed
    • Google Scholar
62. 1. Rosenheck S
    2. Choder M

    (1998) Rpb4, a subunit of RNA polymerase II, enables the enzyme to transcribe at temperature extremes in vitro

    Journal of Bacteriology 180:6187–6192.

    https://doi.org/10.1128/JB.180.23.6187-6192.1998

    • PubMed
    • Google Scholar
63. 1. Sachs AB
    2. Davis RW

    (1989) The poly(A) binding protein is required for poly(A) shortening and 60S ribosomal subunit-dependent translation initiation

    Cell 58:857–867.

    https://doi.org/10.1016/0092-8674(89)90938-0

    • PubMed
    • Google Scholar
64. 1. Schawalder S
    2. Kabani M
    3. Howald I
    4. Choudhury U
    5. Werner M
    6. Shore D
    7. Wade JT
    8. Hall DB
    9. Struhl K

    (2004)

    Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1

    Nature 432:03200ï.

    • Google Scholar
65. 1. Selitrennik M
    2. Duek L
    3. Lotan R
    4. Choder M

    (2006) Nucleocytoplasmic shuttling of the Rpb4p and Rpb7p subunits of Saccharomyces cerevisiae RNA polymerase II by two pathways

    Eukaryotic Cell 5:2092–2103.

    https://doi.org/10.1128/EC.00288-06

    • PubMed
    • Google Scholar
66. 1. Shore D
    2. Zencir S
    3. Albert B

    (2021) Transcriptional control of ribosome biogenesis in yeast: links to growth and stress signals

    Biochemical Society Transactions 49:1589–1599.

    https://doi.org/10.1042/BST20201136

    • PubMed
    • Google Scholar
67. 1. Sigurdsson S
    2. Dirac-Svejstrup AB
    3. Svejstrup JQ

    (2010) Evidence that transcript cleavage is essential for RNA polymerase II transcription and cell viability

    Molecular Cell 38:202–210.

    https://doi.org/10.1016/j.molcel.2010.02.026

    • PubMed
    • Google Scholar
68. 1. Sun M
    2. Schwalb B
    3. Schulz D
    4. Pirkl N
    5. Etzold S
    6. Larivière L
    7. Maier KC
    8. Seizl M
    9. Tresch A
    10. Cramer P

    (2012) Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation

    Genome Research 22:1350–1359.

    https://doi.org/10.1101/gr.130161.111

    • PubMed
    • Google Scholar
69. 1. Timmers HTM
    2. Tora L

    (2018) Transcript Buffering: A Balancing Act between mRNA Synthesis and mRNA Degradation

    Molecular Cell 72:10–17.

    https://doi.org/10.1016/j.molcel.2018.08.023

    • PubMed
    • Google Scholar
70. 1. Trcek T
    2. Larson DR
    3. Moldón A
    4. Query CC
    5. Singer RH

    (2011) Single-molecule mRNA decay measurements reveal promoter- regulated mRNA stability in yeast

    Cell 147:1484–1497.

    https://doi.org/10.1016/j.cell.2011.11.051

    • PubMed
    • Google Scholar
71. 1. Uetz P
    2. Giot L
    3. Cagney G
    4. Mansfield TA
    5. Judson RS
    6. Knight JR
    7. Lockshon D
    8. Narayan V
    9. Srinivasan M
    10. Pochart P
    11. Qureshi-Emili A
    12. Li Y
    13. Godwin B
    14. Conover D
    15. Kalbfleisch T
    16. Vijayadamodar G
    17. Yang M
    18. Johnston M
    19. Fields S
    20. Rothberg JM

    (2000) A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae

    Nature 403:623–627.

    https://doi.org/10.1038/35001009

    • Google Scholar
72. 1. van Nues R
    2. Schweikert G
    3. de Leau E
    4. Selega A
    5. Langford A
    6. Franklin R
    7. Iosub I
    8. Wadsworth P
    9. Sanguinetti G
    10. Granneman S

    (2017) Kinetic CRAC uncovers a role for Nab3 in determining gene expression profiles during stress

    Nature Communications 8:12.

    https://doi.org/10.1038/s41467-017-00025-5

    • PubMed
    • Google Scholar
73. 1. Vera M
    2. Pani B
    3. Griffiths LA
    4. Muchardt C
    5. Abbott CM
    6. Singer RH
    7. Nudler E

    (2014) The translation elongation factor eEF1A1 couples transcription to translation during heat shock response

    eLife 3:e03164.

    https://doi.org/10.7554/eLife.03164

    • PubMed
    • Google Scholar
74. 1. Villanyi Z
    2. Ribaud V
    3. Kassem S
    4. Panasenko OO
    5. Pahi Z
    6. Gupta I
    7. Steinmetz L
    8. Boros I
    9. Collart MA

    (2014) The Not5 subunit of the ccr4-not complex connects transcription and translation

    PLOS Genetics 10:e1004569.

    https://doi.org/10.1371/journal.pgen.1004569

    • PubMed
    • Google Scholar
75. 1. Wan R
    2. Bai R
    3. Zhan X
    4. Shi Y

    (2020) How is precursor messenger RNA spliced by the spliceosome?

    Annual Review of Biochemistry 89:333–358.

    https://doi.org/10.1146/annurev-biochem-013118-111024

    • PubMed
    • Google Scholar
76. 1. Warner JR

    (1999) The economics of ribosome biosynthesis in yeast

    Trends in Biochemical Sciences 24:437–440.

    https://doi.org/10.1016/s0968-0004(99)01460-7

    • PubMed
    • Google Scholar
77. 1. Xiao R
    2. Chen JY
    3. Liang Z
    4. Luo D
    5. Chen G
    6. Lu ZJ
    7. Chen Y
    8. Zhou B
    9. Li H
    10. Du X
    11. Yang Y
    12. San M
    13. Wei X
    14. Liu W
    15. Lécuyer E
    16. Graveley BR
    17. Yeo GW
    18. Burge CB
    19. Zhang MQ
    20. Zhou Y
    21. Fu XD

    (2019) Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription

    Cell 178:107–121.

    https://doi.org/10.1016/j.cell.2019.06.001

    • PubMed
    • Google Scholar
78. 1. Zid BM
    2. O’Shea EK

    (2014) Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast

    Nature 514:117–121.

    https://doi.org/10.1038/nature13578

    • PubMed
    • Google Scholar

Author details

1. Moran Kelbert

   Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

   Contribution

   Data curation, Investigation, Methodology

   Contributed equally with

   Antonio Jordán-Pla and Lola de Miguel-Jiménez

   Competing interests

   No competing interests declared

2. Antonio Jordán-Pla

   Instituto Biotecmed, Facultad de Biológicas, Universitat de València, Burjassot, Spain

   Contribution

   Conceptualization, Formal analysis, Investigation

   Contributed equally with

   Moran Kelbert and Lola de Miguel-Jiménez

   Competing interests

   No competing interests declared

3. Lola de Miguel-Jiménez

   Instituto de Biomedicina de Sevilla, Universidad de Sevilla-CSIC-Hospital Universitario Virgen del Rocío, and Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Seville, Spain

   Contribution

   Data curation, Investigation

   Contributed equally with

   Moran Kelbert and Antonio Jordán-Pla

   Competing interests

   No competing interests declared

4. José García-Martínez

   Instituto Biotecmed, Facultad de Biológicas, Universitat de València, Burjassot, Spain

   Contribution

   Software, Formal analysis, Methodology

   Competing interests

   No competing interests declared

5. Michael Selitrennik

   Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

   Contribution

   Investigation

   Competing interests

   No competing interests declared

6. Adi Guterman

   Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

   Contribution

   Investigation

   Competing interests

   No competing interests declared

7. Noa Henig

   Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

   Contribution

   Investigation

   Competing interests

   No competing interests declared

8. Sander Granneman

   Centre for Engineering Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

   Contribution

   Data curation, Software, Formal analysis

   Competing interests

   No competing interests declared

9. José E Pérez-Ortín

   Instituto Biotecmed, Facultad de Biológicas, Universitat de València, Burjassot, Spain

   Contribution

   Conceptualization, Supervision, Funding acquisition, Investigation, Methodology, Writing – review and editing

   For correspondence

   jose.e.perez@uv.es

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-1992-513X

10. Sebastián Chávez

    Instituto de Biomedicina de Sevilla, Universidad de Sevilla-CSIC-Hospital Universitario Virgen del Rocío, and Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Seville, Spain

    Contribution

    Conceptualization, Supervision, Funding acquisition, Writing – review and editing

    For correspondence

    schavez@us.es

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-8064-4839

11. Mordechai Choder

    Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Contribution

    Conceptualization, Supervision, Funding acquisition, Writing - original draft, Writing – review and editing

    For correspondence

    choder@technion.ac.il

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-0187-2110

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