Helmholtz Gemeinschaft


Exon junction complexes suppress spurious splice sites to safeguard transcriptome integrity

Item Type:Article
Title:Exon junction complexes suppress spurious splice sites to safeguard transcriptome integrity
Creators Name:Boehm, V. and Britto-Borges, T. and Steckelberg, A.L. and Singh, K.K. and Gerbracht, J.V. and Gueney, E. and Blazquez, L. and Altmüller, J. and Dieterich, C. and Gehring, N.H.
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 de-repressed, 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.
Keywords:Alternative Splicing, mRNA Processing, Exon Junction Complex, EJC, Gene Expression, Cryptic Splice Sites
Source:Molecular Cell
Publisher:Cell Press
Page Range:482-495
Date:1 November 2018
Official Publication:https://doi.org/10.1016/j.molcel.2018.08.030
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library