Evidence map›Paper›PMID 36435176›Full record

ArticleMolecular cell2022

Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing.

Yi Zeng, Benjamin J Fair, Huilin Zeng, Aiswarya Krishnamohan, Yichen Hou, Johnathon M Hall, Alexander J Ruthenburg, Yang I Li, Jonathan P Staley

Abstract read
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

  1. Article
  2. Article
  3. Detection of a sequence feature for recursive splicing.bioRxiv : the preprint server for biology · 2026
    Article
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  5. Article
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  7. Article
  8. Article
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  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  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

9 authors.

Yi ZengDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Benjamin J FairDepartment of Medicine, University of Chicago, Chicago, IL 60637, USA.
Huilin Zeng855 Jefferson Ave. Redwood City, CA 94063, USA.
Aiswarya KrishnamohanDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Yichen HouDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Johnathon M HallDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Alexander J RuthenburgDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Yang I LiDepartment of Medicine, University of Chicago, Chicago, IL 60637, USA; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. Electronic address: yangili1@uchicago.edu.
Jonathan P StaleyDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: jstaley@uchicago.edu.

Funding

Mechanisms for Rearranging RNA during Pre-mRNA Splicing - Renewal 01R01GM062264 · NIGMS · UNIVERSITY OF CHICAGO · PI STALEY, JONATHAN P · 2001 to 2019
$5.3M
Novel methods to detect and interpret splicing quantitative trait loci - RenewalR01HG011067 · NHGRI · UNIVERSITY OF CHICAGO · PI Yang Li, JONATHAN P STALEY · 2020 to 2026
$4.2M
Gene Regulatory Non-Coding RNAs in the Human HeartR01HL148719 · NHLBI · UNIVERSITY OF CHICAGO · PI MOSKOWITZ, IVAN PAUL, RUTHENBURG, ALEXANDER JACKSON · 2019 to 2022
$2.3M
Investigating the co-transcriptional impact of genetic variation on gene regulation and diseaseR01GM130738 · NIGMS · UNIVERSITY OF CHICAGO · PI LI, YANG · 2019 to 2023
$2.2M
Defining the mechanisms of epigenetic information flowR35GM145373 · NIGMS · UNIVERSITY OF CHICAGO · PI Alexander Jackson Ruthenburg · 2022 to 2026
$2.1M
Quantitatively probing intra-nucleosomal chromatin variation and functionR01GM115945 · NIGMS · UNIVERSITY OF CHICAGO · PI RUTHENBURG, ALEXANDER JACKSON · 2016 to 2020
$1.6M
NHGRI NIH HHS R01 HG011067NHLBI NIH HHS R01 HL148719NIGMS NIH HHS R01 GM062264NIGMS NIH HHS R01 GM115945NIGMS NIH HHS R01 GM130738NIGMS NIH HHS R35 GM145373
6 · The paper itself

Abstract

Long introns with short exons in vertebrate genes are thought to require spliceosome assembly across exons (exon definition), rather than introns, thereby requiring transcription of an exon to splice an upstream intron. Here, we developed CoLa-seq (co-transcriptional lariat sequencing) to investigate the timing and determinants of co-transcriptional splicing genome wide. Unexpectedly, 90% of all introns, including long introns, can splice before transcription of a downstream exon, indicating that exon definition is not obligatory for most human introns. Still, splicing timing varies dramatically across introns, and various genetic elements determine this variation. Strong U2AF2 binding to the polypyrimidine tract predicts early splicing, explaining exon definition-independent splicing. Together, our findings question the essentiality of exon definition and reveal features beyond intron and exon length that are determinative for splicing timing.

Indexed as

Alternative SplicingRNA SplicingBase SequenceExonsHumansIntronsbranch pointCoLa-seqco-transcriptional splicingexon definitionGC contentintron definitionlariat RNAsmodelingpolypyrimidine tractU2AF

Identifiers

PMID36435176
PMCPMC10448999

What OpenQuestion holds

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Registered trials

None linked

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.