Universität zu Köln

Boehm, Volker ORCID: 0000-0001-7588-9842, Haberman, Nejc ORCID: 0000-0001-9247-4139, Ottens, Franziska ORCID: 0000-0002-0353-2649, Ule, Jernej ORCID: 0000-0002-2452-4277 and Gehring, Niels H. ORCID: 0000-0001-7792-1164 (2014). 3 ' UTR Length and Messenger Ribonucleoprotein Composition Determine Endocleavage Efficiencies at Termination Codons. Cell Reports, 9 (2). S. 555 - 569. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Nonsense-mediated mRNA decay (NMD) degrades different classes of mRNAs, including transcripts with premature termination codons (PTCs). The NMD factor SMG6 initiates degradation of substrate mRNAs by endonucleolytic cleavage. Here, we aim to delineate the cascade of NMD-activating events that culminate in endocleavage. We report that long 3' UTRs elicit SMG6-mediated endonucleolytic degradation. The presence of an exon-junction complex (EJC) within the 3' UTR strongly stimulates endocleavage in a distance-independent manner. The interaction of SMG6 with EJCs is not required for endocleavage. Whereas the core NMD component UPF2 supports endonucleolytic decay of long 3' UTR mRNAs, it is mostly dispensable during EJC-stimulated endocleavage. Using high-throughput sequencing, we map endocleavage positions of different PTC-containing reporter mRNAs and an endogenous NMD substrate to regions directly at and downstream of the termination codon. These results reveal how messenger ribonucleoprotein (mRNP) parameters differentially influence SMG6-executed endonucleolysis and uncover central characteristics of this phenomenon associated with translation termination.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boehm, Volker UNSPECIFIED orcid.org/0000-0001-7588-9842 UNSPECIFIED Haberman, Nejc UNSPECIFIED orcid.org/0000-0001-9247-4139 UNSPECIFIED Ottens, Franziska UNSPECIFIED orcid.org/0000-0002-0353-2649 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:38-425567
DOI:	10.1016/j.celrep.2014.09.012
Journal or Publication Title:	Cell Reports
Volume:	9
Number:	2
Page Range:	S. 555 - 569
Date:	2014
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
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 EXON-JUNCTION COMPLEX; RNA DECAY; ENDONUCLEOLYTIC CLEAVAGE; MAMMALIAN-CELLS; NONSENSE CODONS; UPF1; NMD; SURVEILLANCE; SMG6; PHOSPHORYLATION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42556