Evidence map›Paper›PMID 34389041›Full record

ArticleGenome biology2021

Nanopore sequencing reveals endogenous NMD-targeted isoforms in human cells.

Evangelos D Karousis, Foivos Gypas, Mihaela Zavolan, Oliver Mühlemann

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

48 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  10. BiallelicFrontiers in genetics · 2026
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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

4 authors at 3 institutions in 1 country.

Evangelos D KarousisDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
Foivos GypasFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland.
Mihaela ZavolanBiozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056, Basel, Switzerland.
Oliver MühlemannDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland. oliver.muehlemann@dcb.unibe.ch.ORCID 0000-0003-0657-1368
University of Bern · CHFriedrich Miescher Institute · CHSIB Swiss Institute of Bioinformatics · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNonsense-mediated mRNA decay (NMD) is a eukaryotic, translation-dependent degradation pathway that targets mRNAs with premature termination codons and also regulates the expression of some mRNAs that encode full-length proteins. Although many genes express NMD-sensitive transcripts, identifying them based on short-read sequencing data remains a challenge.

resultsTo identify and analyze endogenous targets of NMD, we apply cDNA Nanopore sequencing and short-read sequencing to human cells with varying expression levels of NMD factors. Our approach detects full-length NMD substrates that are highly unstable and increase in levels or even only appear when NMD is inhibited. Among the many new NMD-targeted isoforms that our analysis identifies, most derive from alternative exon usage. The isoform-aware analysis reveals many genes with significant changes in splicing but no significant changes in overall expression levels upon NMD knockdown. NMD-sensitive mRNAs have more exons in the 3΄UTR and, for those mRNAs with a termination codon in the last exon, the length of the 3΄UTR per se does not correlate with NMD sensitivity. Analysis of splicing signals reveals isoforms where NMD has been co-opted in the regulation of gene expression, though the main function of NMD seems to be ridding the transcriptome of isoforms resulting from spurious splicing events.

conclusionsLong-read sequencing enables the identification of many novel NMD-sensitive mRNAs and reveals both known and unexpected features concerning their biogenesis and their biological role. Our data provide a highly valuable resource of human NMD transcript targets for future genomic and transcriptomic applications.

Indexed as

Nonsense Mediated mRNA DecayCarrier ProteinsCodon, NonsenseEndoribonucleasesExonsGenomicsHeLa CellsHumansNanopore SequencingProtein IsoformsRNA, MessengerRNA SplicingRNA StabilityTelomeraseTranscriptomeCarrier ProteinsCodon, NonsenseEndoribonucleasesProtein IsoformsRNA, MessengerSMG6 protein, humanSMG7 protein, humanTelomerasecDNA sequencingLong-read sequencingmRNA degradationmRNA isoformsNanopore sequencingNMDNonsense-mediated mRNA decaytranscriptomics

Identifiers

PMID34389041
PMCPMC8361881
OpenAlexW3192724755

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LicenceCC BY
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Registered trials

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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.