Transcript-specific characteristics determine the contribution of endo- and exonucleolytic decay pathways during the degradation of nonsense-mediated decay substrates
File(s)
Published version
Author(s)
Ottens, F
Boehm, V
Sibley, CR
Ule, J
Gehring, NH
Type
Journal Article
Abstract
Nonsense-mediated mRNA decay (NMD) controls gene expression by eliminating mRNAs with premature or aberrant translation termination. Degradation of NMD substrates is initiated by the central NMD factor UPF1, which recruits the endonuclease SMG6 and the deadenylation-promoting SMG5/7 complex. The extent to which SMG5/7 and SMG6 contribute to the degradation of individual substrates and their regulation by UPF1 remain elusive. Here we map transcriptome-wide sites of SMG6-mediated endocleavage via 3' fragment capture and degradome sequencing. This reveals that endogenous transcripts can have NMD-eliciting features at various positions, including upstream open reading frames (uORFs), premature termination codons (PTCs) and long 3' UTRs. We find that NMD substrates with PTCs undergo constitutive SMG6-dependent endocleavage, rather than SMG7-dependent exonucleolytic decay. In contrast, the turnover of NMD substrates containing uORFs and long 3' UTRs involves both, SMG6- and SMG7-dependent endo- and exonucleolytic decay, respectively. This suggests that the extent to which SMG6 and SMG7 degrade NMD substrates is determined by the mRNA architecture.
Date Issued
2017-05-01
Date Acceptance
2017-04-17
Citation
RNA, 2017, 23, pp.1224-1236
ISSN
1355-8382
Publisher
Cold Spring Harbor Laboratory Press
Start Page
1224
End Page
1236
Journal / Book Title
RNA
Volume
23
Copyright Statement
© 2017 Ottens et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society
This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/28461625
PII: rna.059659.116
Subjects
NMD
SMG6
decay intermediates
degradome sequencing
endonucleolytic cleavage
Publication Status
Published
Coverage Spatial
United States