1. Chromosomes and Gene Expression
Download icon

The dynamic assembly of distinct RNA polymerase I complexes modulates rDNA transcription

  1. Eva Torreira
  2. Jaime Alegrio Louro
  3. Irene Pazos
  4. Noelia González-Polo
  5. David Gil-Carton
  6. Ana Garcia Duran
  7. Sébastien Tosi
  8. Oriol Gallego  Is a corresponding author
  9. Olga Calvo
  10. Carlos Fernández-Tornero  Is a corresponding author
  1. Centro de Investigaciones Biológicas, Spain
  2. The Barcelona Institute of Science and Technology, Spain
  3. Instituto de Biología Funcional y Genómica, Spain
  4. Cooperative Center for Research in Biosciences CIC bioGUNE, Spain
Research Article
  • Cited 29
  • Views 3,441
  • Annotations
Cite this article as: eLife 2017;6:e20832 doi: 10.7554/eLife.20832

Abstract

Cell growth requires synthesis of ribosomal RNA by RNA polymerase I (Pol I). Binding of initiation factor Rrn3 activates Pol I, fostering recruitment to ribosomal DNA promoters. This fundamental process must be precisely regulated to satisfy cell needs at any time. We present in vivo evidence that, when growth is arrested by nutrient deprivation, cells induce rapid clearance of Pol I-Rrn3 complexes, followed by the assembly of inactive Pol I homodimers. This dual repressive mechanism reverts upon nutrient addition, thus restoring cell growth. Moreover, Pol I dimers also form after inhibition of either ribosome biogenesis or protein synthesis. Our mutational analysis, based on the electron cryomicroscopy structures of monomeric Pol I alone and in complex with Rrn3, underscores the central role of subunits A43 and A14 in the regulation of differential Pol I complexes assembly and subsequent promoter association.

Article and author information

Author details

  1. Eva Torreira

    Centro de Investigaciones Biológicas, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Jaime Alegrio Louro

    Centro de Investigaciones Biológicas, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2800-923X
  3. Irene Pazos

    Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Noelia González-Polo

    Instituto de Biología Funcional y Genómica, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. David Gil-Carton

    Structural Biology Unit, Cooperative Center for Research in Biosciences CIC bioGUNE, Derio, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Ana Garcia Duran

    Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Sébastien Tosi

    Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Oriol Gallego

    Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain
    For correspondence
    oriol.gallego@irbbarcelona.org
    Competing interests
    The authors declare that no competing interests exist.
  9. Olga Calvo

    Instituto de Biología Funcional y Genómica, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Carlos Fernández-Tornero

    Centro de Investigaciones Biológicas, Madrid, Spain
    For correspondence
    cftornero@cib.csic.es
    Competing interests
    The authors declare that no competing interests exist.

Funding

Ministerio de Economía y Competitividad (BFU2013-48374-P)

  • Carlos Fernández-Tornero

Fundación Ramón Areces (-)

  • Carlos Fernández-Tornero

Ministerio de Economía y Competitividad (RYC-2011-07967)

  • Oriol Gallego

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Alan G Hinnebusch, National Institutes of Health, United States

Publication history

  1. Received: August 21, 2016
  2. Accepted: March 6, 2017
  3. Accepted Manuscript published: March 6, 2017 (version 1)
  4. Accepted Manuscript updated: March 8, 2017 (version 2)
  5. Version of Record published: March 22, 2017 (version 3)
  6. Version of Record updated: March 24, 2017 (version 4)

Copyright

© 2017, Torreira et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,441
    Page views
  • 688
    Downloads
  • 29
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cancer Biology
    2. Chromosomes and Gene Expression
    Shou Liu et al.
    Research Article Updated

    ARID1A is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that ARID1A deficiency induces global changes in the epigenetic landscape of enhancers and promoters. These broad and complex effects make it challenging to identify the driving mechanisms of ARID1A deficiency in promoting cancer progression. Here, we identified the anti-senescence effect of Arid1a deficiency in the progression of pancreatic intraepithelial neoplasia (PanIN) by profiling the transcriptome of individual PanINs in a mouse model. In a human cell line model, we found that ARID1A deficiency upregulates the expression of aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which plays an essential role in attenuating the senescence induced by oncogenic KRAS through scavenging reactive oxygen species. As a subunit of the SWI/SNF chromatin remodeling complex, our ATAC sequencing data showed that ARID1A deficiency increases the accessibility of the enhancer region of ALDH1A1. This study provides the first evidence that ARID1A deficiency promotes pancreatic tumorigenesis by attenuating KRAS-induced senescence through the upregulation of ALDH1A1 expression.

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Michael Chas Sumner et al.
    Research Article Updated

    Hundreds of genes interact with the yeast nuclear pore complex (NPC), localizing at the nuclear periphery and clustering with co-regulated genes. Dynamic tracking of peripheral genes shows that they cycle on and off the NPC and that interaction with the NPC slows their sub-diffusive movement. Furthermore, NPC-dependent inter-chromosomal clustering leads to coordinated movement of pairs of loci separated by hundreds of nanometers. We developed fractional Brownian motion simulations for chromosomal loci in the nucleoplasm and interacting with NPCs. These simulations predict the rate and nature of random sub-diffusion during repositioning from nucleoplasm to periphery and match measurements from two different experimental models, arguing that recruitment to the nuclear periphery is due to random sub-diffusion and transient capture by NPCs. Finally, the simulations do not lead to inter-chromosomal clustering or coordinated movement, suggesting that interaction with the NPC is necessary, but not sufficient, to cause clustering.