1. Chromosomes and Gene Expression

The transcriptional elongation rate regulates alternative polyadenylation in yeast

  1. Joseph V Geisberg
  2. Zarmik Moqtaderi
  3. Kevin Struhl  Is a corresponding author
  1. Harvard Medical School, United States
https://doi.org/10.7554/eLife.59810
Share this article
Cite this article
  1. Joseph V Geisberg
  2. Zarmik Moqtaderi
  3. Kevin Struhl
(2020)
The transcriptional elongation rate regulates alternative polyadenylation in yeast
eLife 9:e59810.
https://doi.org/10.7554/eLife.59810
  2. Download BibTeX
  3. Download .RIS

Abstract

Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3' mRNA isoforms for most genes. This altered poly(A) pattern is extremely similar to that observed in cells containing Pol II derivatives with slow elongation rates. Conversely, cells containing derivatives with fast elongation rates show a subtle downstream shift in poly(A) sites. Polyadenylation patterns of many genes are sensitive to both fast and slow elongation rates, and a global shift of poly(A) utilization is strongly linked to increased purine content of sequences flanking poly(A) sites. Pol II processivity is impaired in diauxic cells, but strains with reduced processivity and normal Pol II elongation rates have normal polyadenylation profiles. Thus, Pol II elongation speed is important for poly(A) site selection and for regulating poly(A) patterns in response to environmental conditions.

Data availability

Sequencing data has been deposited in GEO under accession code GSE151196

The following data sets were generated

Article and author information

Author details

  1. Joseph V Geisberg

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.

  2. Zarmik Moqtaderi

    Blavatnik Institute, Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2785-7034

  3. Kevin Struhl

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    For correspondence
    kevin@hms.harvard.edu
    Competing interests
    Kevin Struhl, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4181-7856

Funding

National Institutes of Health (GM 30186)

  • Joseph V Geisberg
  • Zarmik Moqtaderi
  • Kevin Struhl

National Institutes of Health (GM 131801)

  • Joseph V Geisberg
  • Zarmik Moqtaderi
  • Kevin Struhl

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

Copyright

© 2020, Geisberg 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

  • 3,021
    views
  • 407
    downloads
  • 35
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

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)

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

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

  1. Joseph V Geisberg
  2. Zarmik Moqtaderi
  3. Kevin Struhl
(2020)
The transcriptional elongation rate regulates alternative polyadenylation in yeast
eLife 9:e59810.
https://doi.org/10.7554/eLife.59810

Share this article

https://doi.org/10.7554/eLife.59810

Categories and tags

Research organism

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Nucleotide-level linkage of transcriptional elongation and polyadenylation

    Joseph V Geisberg, Zarmik Moqtaderi ... Kevin Struhl
    Research Advance Updated

    Alternative polyadenylation yields many mRNA isoforms whose 3’ termini occur disproportionately in clusters within 3’ untranslated regions. Previously, we showed that profiles of poly(A) site usage are regulated by the rate of transcriptional elongation by RNA polymerase (Pol) II (Geisberg et al., 2020). Pol II derivatives with slow elongation rates confer an upstream-shifted poly(A) profile, whereas fast Pol II strains confer a downstream-shifted poly(A) profile. Within yeast isoform clusters, these shifts occur steadily from one isoform to the next across nucleotide distances. In contrast, the shift between clusters – from the last isoform of one cluster to the first isoform of the next – is much less pronounced, even over large distances. GC content in a region 13–30 nt downstream from isoform clusters correlates with their sensitivity to Pol II elongation rate. In human cells, the upstream shift caused by a slow Pol II mutant also occurs continuously at single nucleotide resolution within clusters but not between them. Pol II occupancy increases just downstream of poly(A) sites, suggesting a linkage between reduced elongation rate and cluster formation. These observations suggest that (1) Pol II elongation speed affects the nucleotide-level dwell time allowing polyadenylation to occur, (2) poly(A) site clusters are linked to the local elongation rate, and hence do not arise simply by intrinsically imprecise cleavage and polyadenylation of the RNA substrate, (3) DNA sequence elements can affect Pol II elongation and poly(A) profiles, and (4) the cleavage/polyadenylation and Pol II elongation complexes are spatially, and perhaps physically, coupled so that polyadenylation occurs rapidly upon emergence of the nascent RNA from the Pol II elongation complex.