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

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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:
CreatorsEmailORCIDORCID Put Code
Boehm, VolkerUNSPECIFIEDorcid.org/0000-0001-7588-9842UNSPECIFIED
Britto-Borges, ThiagoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steckelberg, Anna-LenaUNSPECIFIEDorcid.org/0000-0001-7988-9946UNSPECIFIED
Singh, Kusum K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerbracht, Jennifer V.UNSPECIFIEDorcid.org/0000-0002-3377-4649UNSPECIFIED
Gueney, ElifUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blazquez, LoreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dieterich, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehring, Niels H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
MESSENGER-RNA; GENE-EXPRESSION; CORE COMPLEX; HUMAN RNPS1; REVEALS; VISUALIZATION; DROSOPHILA; DEFINITION; ENHANCERS; EXPANSIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16715

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