Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.

Abstract:

:Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of NMD substrates and their 5'-3' decay intermediates to establish that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Additionally, transcripts from genes encoding multiple snoRNAs often yield alternative transcript isoforms that allow for differential expression of individual coencoded snoRNAs. Based on our findings, we hypothesize that snoRNA host genes need to be highly transcribed to accommodate high levels of snoRNA production and that the expression of individual snoRNAs and their cognate spliced RNA can be uncoupled via alternative splicing and NMD.

journal_name

Genes Dev

journal_title

Genes & development

authors

Lykke-Andersen S,Chen Y,Ardal BR,Lilje B,Waage J,Sandelin A,Jensen TH

doi

10.1101/gad.246538.114

subject

Has Abstract

pub_date

2014-11-15 00:00:00

pages

2498-517

issue

22

eissn

0890-9369

issn

1549-5477

pii

28/22/2498

journal_volume

28

pub_type

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