Evidence map›Paper›PMID 28977470›Full record

ArticleNucleic acids research2017

The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer.

Madhumitha Rengasamy, Fan Zhang, Ajay Vashisht, Won-Min Song, Francesca Aguilo, Yifei Sun, SiDe Li, Weijia Zhang, Bin Zhang, James A Wohlschlegel and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

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2 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 3 countries.

Madhumitha RengasamyDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Fan ZhangDepartment of Medicine, Division of Nephrology, Bioinformatics Laboratory, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ajay VashishtDepartmentof Biological Chemistry and the Institute of Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA.
Won-Min SongDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Francesca AguiloWallenberg Centre for Molecular Medicine, Department of Medical Biosciences, University of Umeå, Försörjningsvägen 19073, Umeå, Sweden.
Yifei SunDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
SiDe LiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Weijia ZhangDepartment of Medicine, Division of Nephrology, Bioinformatics Laboratory, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
James A WohlschlegelDepartmentof Biological Chemistry and the Institute of Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA.
Martin J WalshDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Icahn School of Medicine at Mount Sinai · USUniversity of California, Los Angeles · USCenter for Life Sciences · CNUmeå University · SE

Funding

Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
NIH HHS S10 OD018522
6 · The paper itself

Abstract

We observed overexpression and increased intra-nuclear accumulation of the PRMT5/WDR77 in breast cancer cell lines relative to immortalized breast epithelial cells. Utilizing mass spectrometry and biochemistry approaches we identified the Zn-finger protein ZNF326, as a novel interaction partner and substrate of the nuclear PRMT5/WDR77 complex. ZNF326 is symmetrically dimethylated at arginine 175 (R175) and this modification is lost in a PRMT5 and WDR77-dependent manner. Loss of PRMT5 or WDR77 in MDA-MB-231 cells leads to defects in alternative splicing, including inclusion of A-T rich exons in target genes, a phenomenon that has previously been observed upon loss of ZNF326. We observed that the alternatively spliced transcripts of a subset of these genes, involved in proliferation and tumor cell migration like REPIN1/AP4, ST3GAL6, TRNAU1AP and PFKM are degraded upon loss of PRMT5. In summary, we have identified a novel mechanism through which the PRMT5/WDR77 complex maintains the balance between splicing and mRNA stability through methylation of ZNF326.

Indexed as

Alternative SplicingBreast NeoplasmsCarrier ProteinsCell LineCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunoblottingMCF-7 CellsProtein-Arginine N-MethyltransferasesProtein BindingReverse Transcriptase Polymerase Chain ReactionTandem Mass SpectrometryTranscription FactorsCarrier ProteinsPRMT5 protein, humanProtein-Arginine N-MethyltransferasesTranscription FactorsWDR77 protein, humanZNF326 protein, human

Identifiers

PMID28977470
PMCPMC5737218
OpenAlexW2748589070

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.