Universität zu Köln

Fatscher, Tobias and Gehring, Niels H. ORCID: 0000-0001-7792-1164 (2016). Harnessing short poly(A)-binding protein-interacting peptides for the suppression of nonsense-mediated mRNA decay. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Nonsense-mediated mRNA decay (NMD) is a cellular process that eliminates messenger RNA (mRNA) substrates with premature translation termination codons (PTCs). In addition, NMD regulates the expression of a number of physiological mRNAs, for example transcripts containing long 3'UTRs. Current models implicate the interaction between cytoplasmic poly(A)-binding protein (PABPC1) and translation termination in NMD. Accordingly, PABPC1 present within close proximity of a termination codon antagonizes NMD. Here, we use reporter mRNAs with different NMD-inducing 3'UTRs to establish a general NMD-inhibiting property of PABPC1. NMD-inhibition is not limited to PABPC1, but can also be achieved by peptides consisting of the PABP-interacting motif 2 (PAM2) of different proteins when recruited to an NMD-inhibiting position of NMD reporter transcripts. The short PAM2 peptides efficiently suppress NMD activated by a long 3'UTR, an exon-junction complex (EJC) and individual EJC components, and stabilize a PTC-containing beta-globin mRNA. In conclusion, our results establish short PABPC1-recruiting peptides as potent but position-dependent inhibitors of mammalian NMD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fatscher, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehring, Niels H. UNSPECIFIED orcid.org/0000-0001-7792-1164 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-255534
DOI:	10.1038/srep37311
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
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; C-TERMINAL DOMAIN; EUKARYOTIC TRANSLATION; INITIATION-FACTOR; BINDING-PROTEIN; UPF1 GENE; SURVEILLANCE; PABC; IDENTIFICATION; RECOGNITION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25553