Universität zu Köln

Boehm, Volker ORCID: 0000-0001-7588-9842, Britto-Borges, Thiago, Steckelberg, Anna-Lena ORCID: 0000-0001-7988-9946, Singh, Kusum K., Gerbracht, Jennifer V. ORCID: 0000-0002-3377-4649, Gueney, Elif, Blazquez, Lorea, Altmueller, Janine, Dieterich, Christoph and Gehring, Niels H. (2018). Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity. Mol. Cell, 72 (3). S. 482 - 503. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

Full text not available from this repository.

Abstract

Productive splicing of human precursor messenger RNAs (pre-mRNAs) requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryptic SS are insufficiently explored. Here, we find that many aberrant exonic SS are efficiently silenced by the exon junction complex (EJC), a multi-protein complex that is deposited on spliced mRNA near the exon-exon junction. Upon depletion of EJC proteins, cryptic SS are derepressed, leading to the mis-splicing of a broad set of mRNAs. Mechanistically, the EJC-mediated recruitment of the splicing regulator RNPS1 inhibits cryptic 5'SS usage, while the deposition of the EJC core directly masks reconstituted 3'SS, thereby precluding transcript disintegration. Thus, the EJC protects the transcriptome of mammalian cells from inadvertent loss of exonic sequences and safeguards the expression of intact, full-length mRNAs.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boehm, Volker UNSPECIFIED orcid.org/0000-0001-7588-9842 UNSPECIFIED Britto-Borges, Thiago UNSPECIFIED UNSPECIFIED UNSPECIFIED Steckelberg, Anna-Lena UNSPECIFIED orcid.org/0000-0001-7988-9946 UNSPECIFIED Singh, Kusum K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerbracht, Jennifer V. UNSPECIFIED orcid.org/0000-0002-3377-4649 UNSPECIFIED Gueney, Elif UNSPECIFIED UNSPECIFIED UNSPECIFIED Blazquez, Lorea UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehring, Niels H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-167156
DOI:	10.1016/j.molcel.2018.08.030
Journal or Publication Title:	Mol. Cell
Volume:	72
Number:	3
Page Range:	S. 482 - 503
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
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; GENE-EXPRESSION; CORE COMPLEX; HUMAN RNPS1; REVEALS; VISUALIZATION; DROSOPHILA; DEFINITION; ENHANCERS; EXPANSION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16715