Evidence map›Paper›PMID 22624609›Full record

ArticleGenome biology2012

Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns.

Joachim Weischenfeldt, Johannes Waage, Geng Tian, Jing Zhao, Inge Damgaard, Janus Schou Jakobsen, Karsten Kristiansen, Anders Krogh, Jun Wang, Bo T Porse

Abstract read
In one paragraph

Article in Genome biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

97 citing papers in PubMed.

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  19. Global impact of aberrant splicing on human gene expression levels.bioRxiv : the preprint server for biology · 2023
    Article
  20. Article

37 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.

Joachim WeischenfeldtThe Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, DK2200 Copenhagen, Denmark. bo.porse@finsenlab.dk
Johannes Waage
Geng Tian
Jing Zhao
Inge Damgaard
Janus Schou Jakobsen
Karsten Kristiansen
Anders Krogh
Jun Wang
Bo T Porse

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, the extent to which loss of NMD causes extensive deregulation of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2.

resultsWe developed a bioinformatic pipeline that maps RNA-seq data to a combinatorial exon database, predicts NMD-susceptibility for mRNA isoforms and calculates the distribution of major splice isoform classes. We present a catalog of NMD-regulated alternative splicing events, showing that isoforms of 30% of all expressed genes are upregulated in NMD-deficient cells and that NMD targets all major splicing classes. Importantly, NMD-dependent effects are not restricted to premature termination codon+ isoforms but also involve an abundance of splicing events that do not generate premature termination codons. Supporting their functional importance, the latter events are associated with high intronic conservation.

conclusionsOur data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel insights into its role in core- and tissue-specific regulation of gene expression. Thus, our study extends the importance of NMD from an mRNA quality pathway to a regulator of several layers of gene expression.

Indexed as

Alternative SplicingNonsense Mediated mRNA DecayAnimalsCodon, NonsenseGenomeMaleMammalsMiceRNA, MessengerCodon, NonsenseRNA, Messenger

Identifiers

PMID22624609
PMCPMC3446288

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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.