Evidence map›Paper›PMID 36421680›Full record

ArticleeLife2022

Nucleotide-level linkage of transcriptional elongation and polyadenylation.

Joseph V Geisberg, Zarmik Moqtaderi, Nova Fong, Benjamin Erickson, David L Bentley, Kevin Struhl

Abstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Co-transcriptional gene regulation in eukaryotes and prokaryotes.Nature reviews. Molecular cell biology · 2024
    Review
  10. Chromatin regulates alternative polyadenylation via the RNA polymerase II elongation rate.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Review
  12. Article
  13. Article
  14. mRNA initiation and termination are spatially coordinated.bioRxiv : the preprint server for biology · 2024
    Article
  15. Review
  16. Article
  17. Review
  18. Condition-specific 3' mRNA isoform half-lives and stability elements in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Joseph V Geisberg *Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
Zarmik Moqtaderi *Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.ORCID 0000-0002-2785-7034
Nova FongRNA Bioscience Initiative, Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States.
Benjamin EricksonRNA Bioscience Initiative, Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States.
David L BentleyRNA Bioscience Initiative, Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States.
Kevin StruhlDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.ORCID 0000-0002-4181-7856

Funding

MOLECULAR MECHANISMS OF YEAST TRANSCRIPTIONAL INITIATIONR01GM030186 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI STRUHL, KEVIN · 1985 to 2018
$13.6M
Mechanism of yeast gene regulationR35GM131801 · NIGMS · HARVARD MEDICAL SCHOOL · PI KEVIN STRUHL · 2019 to 2026
$6.4M
Coupling of transcription elongation and termination with pre-mRNA processingR35GM144336 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI DAVID L BENTLEY · 2022 to 2026
$2.5M
Coupling of transcription with nascent pre-mRNA metabolismR35GM118051 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI BENTLEY, DAVID L · 2016 to 2020
$2.2M
MECHANISMS OF YEAST TRANSCRIPTIONAL INITITATIONR37GM030186 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI STRUHL, KEVIN · 1993 to 2002
$2.1M
NIGMS NIH HHS R01 GM030186NIGMS NIH HHS R35 GM118051NIGMS NIH HHS R35 GM131801NIGMS NIH HHS R35 GM144336NIGMS NIH HHS R37 GM030186
6 · The paper itself

Abstract

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.

Indexed as

NucleotidesPolyadenylation3' Untranslated RegionsHumansPoly ARNA Polymerase IISaccharomyces cerevisiaeTranscription, Genetic3' Untranslated RegionsNucleotidesPoly ARNA Polymerase II3' end formationchromosomescleavage/polyadenylation machinerygene expressiongeneticsgenomicshumanpolyadenylationRNA polymerase IIS. cerevisiaetranscriptional elongation

Identifiers

PMID36421680
PMCPMC9721619

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.