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

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...

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Veröffentlicht in:Genes & development 2014-11, Vol.28 (22), p.2498-2517
Hauptverfasser: Lykke-Andersen, Søren, Chen, Yun, Ardal, Britt R, Lilje, Berit, Waage, Johannes, Sandelin, Albin, Jensen, Torben Heick
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container_end_page 2517
container_issue 22
container_start_page 2498
container_title Genes & development
container_volume 28
creator Lykke-Andersen, Søren
Chen, Yun
Ardal, Britt R
Lilje, Berit
Waage, Johannes
Sandelin, Albin
Jensen, Torben Heick
description 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.
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Endonucleases - metabolism
HEK293 Cells
Humans
Nonsense Mediated mRNA Decay - genetics
Nonsense Mediated mRNA Decay - physiology
Protein Isoforms
Research Paper
RNA Splicing
RNA, Small Nucleolar - metabolism
Telomerase - genetics
Telomerase - metabolism
title Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes
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