Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes
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Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes. / Lykke-Andersen, Søren; Chen, Yun; Ardal, Britt; Lilje, Berit; Waage, Johannes Eichler; Sandelin, Albin Gustav; Jensen, Torben Heick.
I: Genes & Development, Bind 28, 2014, s. 2498-2517.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes
AU - Lykke-Andersen, Søren
AU - Chen, Yun
AU - Ardal, Britt
AU - Lilje, Berit
AU - Waage, Johannes Eichler
AU - Sandelin, Albin Gustav
AU - Jensen, Torben Heick
N1 - © 2014 Lykke-Andersen et al.; Published by Cold Spring Harbor Laboratory Press.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1101/gad.246538.114
DO - 10.1101/gad.246538.114
M3 - Journal article
C2 - 25403180
VL - 28
SP - 2498
EP - 2517
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
ER -
ID: 127624047