Evidence map›Paper›PMID 34174817›Full record

ArticleBMC genomics2021

LABRAT reveals association of alternative polyadenylation with transcript localization, RNA binding protein expression, transcription speed, and cancer survival.

Raeann Goering, Krysta L Engel, Austin E Gillen, Nova Fong, David L Bentley, J Matthew Taliaferro

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 44 citations in OpenAlex.

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  13. ThrScience advances · 2024
    Article
  14. Co-transcriptional gene regulation in eukaryotes and prokaryotes.Nature reviews. Molecular cell biology · 2024
    Review
  15. 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
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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 at 1 institution in 1 country.

Raeann Goering *Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Krysta L Engel *Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Austin E GillenRNA Bioscience Initiative, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Nova FongDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
David L BentleyDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Matthew TaliaferroDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. matthew.taliaferro@cuanschutz.edu.ORCID http://orcid.org/0000-0001-7580-1433
University of Colorado Anschutz Medical Campus · US

Funding

Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)T32GM136444 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MICHAEL A MCMURRAY, Rytis Prekeris · 2020 to 2026
$3.7M
Understanding the regulatory language of RNA localizationR35GM133385 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Jefferson Matthew Taliaferro · 2019 to 2026
$3.4M
Predoctoral Training Program in Molecular BiologyT32GM008730 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI PREKERIS, RYTIS, SCLAFANI, ROBERT A · 1999 to 2019
$3.3M
Coupling of transcription with nascent pre-mRNA metabolismR35GM118051 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI BENTLEY, DAVID L · 2016 to 2020
$2.2M
Deciphering the nanomaterial uptake in a bystander manner invoked by co-administration of functionalized nanoparticlesR01GM133885 · NIGMS · UNIVERSITY OF MINNESOTA · PI PANG, HONGBO · 2019 to 2022
$1.2M
NIGMS NIH HHS R35-GM118051NIGMS NIH HHS R35 GM133385NIGMS NIH HHS R35-GM133885NIGMS NIH HHS T32 GM008730NIGMS NIH HHS T32-GM008730NIGMS NIH HHS T32 GM136444
6 · The paper itself

Abstract

backgroundThe sequence content of the 3' UTRs of many mRNA transcripts is regulated through alternative polyadenylation (APA). The study of this process using RNAseq data, though, has been historically challenging.

resultsTo combat this problem, we developed LABRAT, an APA isoform quantification method. LABRAT takes advantage of newly developed transcriptome quantification techniques to accurately determine relative APA site usage and how it varies across conditions. Using LABRAT, we found consistent relationships between gene-distal APA and subcellular RNA localization in multiple cell types. We also observed connections between transcription speed and APA site choice as well as tumor-specific transcriptome-wide shifts in APA isoform abundance in hundreds of patient-derived tumor samples that were associated with patient prognosis. We investigated the effects of APA on transcript expression and found a weak overall relationship, although many individual genes showed strong correlations between relative APA isoform abundance and overall gene expression. We interrogated the roles of 191 RNA-binding proteins in the regulation of APA isoforms, finding that dozens promote broad, directional shifts in relative APA isoform abundance both in vitro and in patient-derived samples. Finally, we find that APA site shifts in the two classes of APA, tandem UTRs and alternative last exons, are strongly correlated across many contexts, suggesting that they are coregulated.

conclusionsWe conclude that LABRAT has the ability to accurately quantify APA isoform ratios from RNAseq data across a variety of sample types. Further, LABRAT is able to derive biologically meaningful insights that connect APA isoform regulation to cellular and molecular phenotypes.

Indexed as

NeoplasmsPolyadenylation3' Untranslated RegionsHumansRNA-Binding ProteinsRNA, Messenger3' Untranslated RegionsRNA-Binding ProteinsRNA, Messenger

Identifiers

PMID34174817
PMCPMC8234626
OpenAlexW3176141851

What OpenQuestion holds

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LicenceCC BY
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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.