Evidence map›Paper›PMID 25452276›Full record

ArticleGenes & development2014

Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate.

Nova Fong, Hyunmin Kim, Yu Zhou, Xiong Ji, Jinsong Qiu, Tassa Saldi, Katrina Diener, Ken Jones, Xiang-Dong Fu, David L Bentley

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers.

0numbers the graph read from it
0cells of the map it votes in
188citing 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

188 citing papers in PubMed, 307 citations in OpenAlex.

  1. Article
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  3. YTHDC1 recognizes METTL16-dependent mProceedings of the National Academy of Sciences of the United States of America · 2026
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  9. Extensive splicing deficiency in a degenerating mating-type chromosome.bioRxiv : the preprint server for biology · 2025
    Article
  10. Article
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  12. CAR-SPLASH identifies nascent pre-mRNA structures implicated in kinetic coupling and alternative splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
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  16. Review
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  18. Review
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  20. Review

128 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Nova FongDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA;
Hyunmin KimDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA;
Yu ZhouDepartment of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California at San Diego, San Diego, California 92093, USA.
Xiong JiDepartment of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California at San Diego, San Diego, California 92093, USA.
Jinsong QiuDepartment of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California at San Diego, San Diego, California 92093, USA.
Tassa SaldiDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA;
Katrina DienerDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA;
Ken JonesDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA;
Xiang-Dong FuDepartment of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California at San Diego, San Diego, California 92093, USA.
David L BentleyDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA; david.bentley@ucdenver.edu.
University of Colorado Denver · USUniversity of California, San Diego · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
FUNCTION &REGULATION OF THE HUMAN SPLICING FACTOR SC35R01GM049369 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FU, XIANG-DONG · 1993 to 2018
$7.2M
Coupling of Transcription with Pre-mRNA MetabolismR01GM058613 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI BENTLEY, DAVID L · 1999 to 2014
$5.5M
NCI NIH HHS P30 CA046934NIGMS NIH HHS GM49369NIGMS NIH HHS GM58613NIGMS NIH HHS R01 GM049369NIGMS NIH HHS R01 GM058613
6 · The paper itself

Abstract

Alternative splicing modulates expression of most human genes. The kinetic model of cotranscriptional splicing suggests that slow elongation expands and that fast elongation compresses the "window of opportunity" for recognition of upstream splice sites, thereby increasing or decreasing inclusion of alternative exons. We tested the model using RNA polymerase II mutants that change average elongation rates genome-wide. Slow and fast elongation affected constitutive and alternative splicing, frequently altering exon inclusion and intron retention in ways not predicted by the model. Cassette exons included by slow and excluded by fast elongation (type I) have weaker splice sites, shorter flanking introns, and distinct sequence motifs relative to "slow-excluded" and "fast-included" exons (type II). Many rate-sensitive exons are misspliced in tumors. Unexpectedly, slow and fast elongation often both increased or both decreased inclusion of a particular exon or retained intron. These results suggest that an optimal rate of transcriptional elongation is required for normal cotranscriptional pre-mRNA splicing.

Indexed as

RNA SplicingExonsHEK293 CellsHumansIntronsMutationRNA Polymerase IIRNA PrecursorsTranscription Elongation, GeneticRNA Polymerase IIRNA Precursorsalternative splicingcotranscriptional splicingintron retentionkinetic couplingtranscription elongation rate

Identifiers

PMID25452276
PMCPMC4248296
OpenAlexW2049022227

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.