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Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity

Boehm, V; Britto-Borges, T; Steckelberg, A-L; Singh, KK; Gerbracht, JV; Gueney, E; Blazquez, L; ... Gehring, NH; + view all (2018) Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity. Molecular Cell , 72 (3) pp. 482-495. 10.1016/j.molcel.2018.08.030. Green open access

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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 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.

Type: Article
Title: Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.molcel.2018.08.030
Publisher version: https://doi.org/10.1016/j.molcel.2018.08.030
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: EJC, alternative splicing, cryptic splice sites, exon junction complex, gene expression, mRNA processing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10063339
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