Evidence map›Paper›PMID 27288314›Full record

ArticleRNA (New York, N.Y.)2016

Multiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2.

Niroshika M Keppetipola, Kyu-Hyeon Yeom, Adrian L Hernandez, Tessa Bui, Shalini Sharma, Douglas L Black

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

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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 3 institutions in 1 country.

Niroshika M KeppetipolaCalifornia State University Fullerton, Department of Chemistry and Biochemistry, Fullerton, California 92831, USA.
Kyu-Hyeon YeomDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
Adrian L HernandezDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
Tessa BuiCalifornia State University Fullerton, Department of Chemistry and Biochemistry, Fullerton, California 92831, USA.
Shalini SharmaDepartment of Basic Medical Sciences, University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona 85004, USA.
Douglas L BlackDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.ORCID 0000-0002-2705-8187
University of California, Los Angeles · USCalifornia State University, Fullerton · USUniversity of Arizona · US

Funding

UCLA MSD ProgramR25GM055052 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BARBER, PAUL HENRY, HASSON, TAMA W. · 1996 to 2021
$9.2M
The Regulation of Neuronal Exon SplicingR01GM049662 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L · 1998 to 2019
$6.5M
Examining role of splicing factor mutations in myelodysplastic syndrome (PQ11)R21CA170786 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHARMA, SHALINI · 2012 to 2013
$366k
Biochemical Characterization of the splicing regulation of nPTBF32GM093533 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI M KEPPETIPOLA, NIROSHIKA A · 2010 to 2011
$99k
NCI NIH HHS R21 CA170786NIGMS NIH HHS F32 GM093533NIGMS NIH HHS R01 GM049662NIGMS NIH HHS R25 GM055052
6 · The paper itself

Abstract

Most human genes generate multiple protein isoforms through alternative pre-mRNA splicing, but the mechanisms controlling alternative splicing choices by RNA binding proteins are not well understood. These proteins can have multiple paralogs expressed in different cell types and exhibiting different splicing activities on target exons. We examined the paralogous polypyrimidine tract binding proteins PTBP1 and PTBP2 to understand how PTBP1 can exhibit greater splicing repression activity on certain exons. Using both an in vivo coexpression assay and an in vitro splicing assay, we show that PTBP1 is more repressive than PTBP2 per unit protein on a target exon. Constructing chimeras of PTBP1 and 2 to determine amino acid features that contribute to their differential activity, we find that multiple segments of PTBP1 increase the repressive activity of PTBP2. Notably, when either RRM1 of PTBP2 or the linker peptide separating RRM2 and RRM3 are replaced with the equivalent PTBP1 sequences, the resulting chimeras are highly active for splicing repression. These segments are distinct from the known region of interaction for the PTBP1 cofactors Raver1 and Matrin3 in RRM2. We find that RRM2 of PTBP1 also increases the repression activity of an otherwise PTBP2 sequence, and that this is potentially explained by stronger binding by Raver1. These results indicate that multiple features over the length of the two proteins affect their ability to repress an exon.

Indexed as

RNA SplicingAnimalsCells, CulturedExonsHumansPolypyrimidine Tract-Binding ProteinProtein ConformationPolypyrimidine Tract-Binding Proteinalternative splicingRNA binding proteins

Identifiers

PMID27288314
PMCPMC4931110
OpenAlexW2418342455

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.