Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways

Colombo, Martino; Karousis, Evangelos D.; Bourquin, Joëll; Bruggmann, Rémy; Mühlemann, Oliver (2017). Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways. RNA - a publication of the RNA Society, 23(2), pp. 189-201. Cold Spring Harbor Laboratory Press 10.1261/rna.059055.116

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Besides degrading aberrant mRNAs that harbor a premature translation termination codon (PTC), nonsense-mediated mRNA decay (NMD) also targets many seemingly "normal" mRNAs that encode for full-length proteins. To identify a bona fide set of such endogenous NMD targets in human cells, we applied a meta-analysis approach in which we combined transcriptome profiling of knockdowns and rescues of the three NMD factors UPF1, SMG6 and SMG7. We provide evidence that this combinatorial approach identifies NMD-targeted transcripts more reliably than previous attempts that focused on inactivation of single NMD factors. Our data revealed that SMG6 and SMG7 act on essentially the same transcripts, indicating extensive redundancy between the endo- and exonucleolytic decay routes. Besides mRNAs, we also identified as NMD targets many long non-coding RNAs as well as miRNA and snoRNA host genes. The NMD target feature with the most predictive value is an intron in the 3' UTR, followed by the presence of upstream open reading frames (uORFs) and long 3' UTRs. Furthermore, the 3' UTRs of NMD-targeted transcripts tend to have an increased GC content and to be phylogenetically less conserved when compared to 3' UTRs of NMD insensitive transcripts.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
08 Faculty of Science > Department of Biology > Bioinformatics

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Colombo, Martino; Karousis, Evangelos; Bruggmann, Rémy and Mühlemann, Oliver

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1355-8382

Publisher:

Cold Spring Harbor Laboratory Press

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

24 Jan 2017 10:13

Last Modified:

24 Jan 2017 10:13

Publisher DOI:

10.1261/rna.059055.116

PubMed ID:

27864472

BORIS DOI:

10.7892/boris.92480

URI:

https://boris.unibe.ch/id/eprint/92480

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