Evidence map›Paper›PMID 25906188›Full record

ArticlePLoS genetics2015

Systematic profiling of poly(A)+ transcripts modulated by core 3' end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation.

Wencheng Li, Bei You, Mainul Hoque, Dinghai Zheng, Wenting Luo, Zhe Ji, Ji Yeon Park, Samuel I Gunderson, Auinash Kalsotra, James L Manley and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% of its field
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

186 citing papers in PubMed, 1 synthesis or guideline pooled it, 274 citations in OpenAlex.

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126 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

11 authors at 4 institutions in 1 country.

Wencheng LiDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America; Rutgers Cancer Institute of New Jersey, Newark, New Jersey, United States of America.
Bei YouDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
Mainul HoqueDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
Dinghai ZhengDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America; Rutgers Cancer Institute of New Jersey, Newark, New Jersey, United States of America.
Wenting LuoDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America; Rutgers Graduate School of Biomedical Sciences, Newark, New Jersey, United States of America.
Zhe JiDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America; Rutgers Graduate School of Biomedical Sciences, Newark, New Jersey, United States of America.
Ji Yeon ParkDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
Samuel I GundersonDepartment of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
Auinash KalsotraDepartments of Biochemistry and Medical Biochemistry, University of Illinois, Urbana, Illinois, United States of America.
James L ManleyDepartment of Biological Sciences, Columbia University, New York, New York, United Staes of America.
Bin TianDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America; Rutgers Cancer Institute of New Jersey, Newark, New Jersey, United States of America; Rutgers Graduate School of Biomedical Sciences, Newark, New Jersey, United States of America.
Rutgers, The State University of New Jersey · USRutgers New Jersey Medical SchoolColumbia University · USUniversity of Illinois Urbana-Champaign · US

Funding

Regulation of Alternative Cleavage and PolyadenylationR01GM084089 · NIGMS · WISTAR INSTITUTE · PI TIAN, BIN · 2008 to 2023
$6.7M
Post-transcriptional mechanisms of gene regulation in cardiac cell growth and developmentR01HL126845 · NHLBI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KALSOTRA, AUINASH · 2015 to 2023
$3.5M
NHLBI NIH HHS R01 HL126845NIGMS NIH HHS R01 GM084089
6 · The paper itself

Abstract

Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3' untranslated regions (3'UTRs) and/or coding sequences. How core cleavage/polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3'UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1 and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI-25/68 or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly inhibiting C/P events in introns near the 5' end of gene and U2 suppressing those in introns with features for efficient splicing. Furthermore, PABPN1 inhibits expression of transcripts with pAs near the transcription start site (TSS), a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results support an APA code where an APA event in a given cellular context is regulated by a number of parameters, including relative location to the TSS, splicing context, distance between competing pAs, surrounding cis elements and concentrations of core C/P factors.

Indexed as

3' Untranslated RegionsCell DifferentiationExonsGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansIntronsPoly(A)-Binding Protein IPolyadenylationRNA, MessengerRNA SplicingRNA Stability3' Untranslated RegionsPABPN1 protein, humanPoly(A)-Binding Protein IRNA, Messenger

Identifiers

PMID25906188
PMCPMC4407891
OpenAlexW1973159925

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.