Pervasive transcription fine-tunes replication origin activity

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Abstract

RNA polymerase (RNAPII) transcription occurs pervasively, raising the important question of its functional impact on other DNA-associated processes, including replication. In budding yeast, replication originates from Autonomously Replicating Sequences (ARSs), generally located in intergenic regions. The influence of transcription on ARSs function has been studied for decades, but these earlier studies have neglected the role of non-annotated transcription. We studied the relationships between pervasive transcription and replication origin activity using high-resolution transcription maps. We show that ARSs alter the pervasive transcription landscape by pausing and terminating neighboring RNAPII transcription, thus limiting the occurrence of pervasive transcription within origins. We propose that quasi-symmetrical binding of the ORC complex to ARS borders and/or pre-RC formation are responsible for pausing and termination. We show that low, physiological levels of pervasive transcription impact the function of replication origins. Overall, our results have important implications for understanding the impact of genomic location on origin function.

Data availability

All data analyzed in this manuscript have been previously published and appropriate GEO accession codes and references have been provided.

The following previously published data sets were used

(2014) Genome-wide mapping of yeast RNA polymerase II termination.
NCBI Gene Expression Omnibus, GSE56435.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56435
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(2018) CRAC of yeast RNA polymerase II in various thermosensitive strains at permissive and non-permissive temperature and anchor-away strains with the addition of rapamycin.
NCBI Gene Expression Omnibus, GSE97913.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97913
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3. Gillespie A
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5. Chanfreau GF
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NCBI Gene Expression Omnibus, GSE75586.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75586

Article and author information

Author details

Tito Candelli

Institut Jacques Monod, CNRS UMR 7592, Université Paris-Diderot, Paris, France

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2440-6032
Julien Gros

Institut Jacques Monod, CNRS UMR 7592, Université Paris-Diderot, Paris Cedex 13, France

For correspondence
julien.gros@ijm.fr

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8316-0207
Domenico Libri

Institut Jacques Monod, CNRS UMR 7592, Université Paris-Diderot, Paris, France

For correspondence
domenico.libri@ijm.fr

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6728-0594

Funding

Centre National de la Recherche Scientifique

Domenico Libri

Fondation pour la Recherche Médicale (F.R.M. programme équipes 2013)

Domenico Libri

Agence Nationale de la Recherche (Grant ANR-16-CE12-0022-01)

Domenico Libri

Labex Who Am I? (ANR-11-LABX-0071)

Domenico Libri

French Ministry of Research (Fellowship)

Tito Candelli

Ligue Nationale Contre le Cancer (GB/MA/CD/IQ - 12031)

Julien Gros

Labex Who Am I? (ANR-11-IDEX-0005-02)

Domenico Libri

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

Copyright

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.