Universität zu Köln

Ottens, Franziska ORCID: 0000-0002-0353-2649, Boehm, Volker ORCID: 0000-0001-7588-9842, Sibley, Christopher R., Ule, Jernej ORCID: 0000-0002-2452-4277 and Gehring, Niels H. ORCID: 0000-0001-7792-1164 (2017). Transcript-specific characteristics determine the contribution of endo- and exonucleolytic decay pathways during the degradation of nonsense-mediated decay substrates. RNA, 23 (8). S. 1224 - 1237. COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. ISSN 1469-9001

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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 remains 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 NMDeliciting 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ottens, Franziska UNSPECIFIED orcid.org/0000-0002-0353-2649 UNSPECIFIED Boehm, Volker UNSPECIFIED orcid.org/0000-0001-7588-9842 UNSPECIFIED Sibley, Christopher R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ule, Jernej UNSPECIFIED orcid.org/0000-0002-2452-4277 UNSPECIFIED Gehring, Niels H. UNSPECIFIED orcid.org/0000-0001-7792-1164 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-224318
DOI:	10.1261/rna.059659.116
Journal or Publication Title:	RNA
Volume:	23
Number:	8
Page Range:	S. 1224 - 1237
Date:	2017
Publisher:	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Place of Publication:	COLD SPRING HARBOR
ISSN:	1469-9001
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESSENGER-RNA DECAY; ENDONUCLEOLYTIC CLEAVAGE; SMG5-SMG7 HETERODIMER; SURVEILLANCE COMPLEX; GLOBAL ANALYSIS; HUMAN-CELLS; SMG6; UPF1; NMD; TERMINATION Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22431