Cargando…

The Exon Junction Complex and intron removal prevent re-splicing of mRNA

Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, splice sites (SS). However, the evolutionary generality of this remains unclear. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cry...

Descripción completa

Detalles Bibliográficos
Autores principales: Joseph, Brian, Lai, Eric C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184009/
https://www.ncbi.nlm.nih.gov/pubmed/34033644
http://dx.doi.org/10.1371/journal.pgen.1009563
_version_ 1783704502527852544
author Joseph, Brian
Lai, Eric C.
author_facet Joseph, Brian
Lai, Eric C.
author_sort Joseph, Brian
collection PubMed
description Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, splice sites (SS). However, the evolutionary generality of this remains unclear. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cryptic SS, even though most bear weak splicing motifs and are seemingly incompetent. Mechanistically, the EJC directly conceals cryptic splicing elements by virtue of its position-specific recruitment, preventing aberrant SS definition. Unexpectedly, we discover the EJC inhibits scores of regenerated 5’ and 3’ recursive SS on segments that have already undergone splicing, and that loss of EJC regulation triggers faulty resplicing of mRNA. An important corollary is that certain intronless cDNA constructs yield unanticipated, truncated transcripts generated by resplicing. We conclude the EJC has conserved roles to defend transcriptome fidelity by (1) repressing illegitimate splice sites on pre-mRNAs, and (2) preventing inadvertent activation of such sites on spliced segments.
format Online
Article
Text
id pubmed-8184009
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-81840092021-06-21 The Exon Junction Complex and intron removal prevent re-splicing of mRNA Joseph, Brian Lai, Eric C. PLoS Genet Research Article Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, splice sites (SS). However, the evolutionary generality of this remains unclear. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cryptic SS, even though most bear weak splicing motifs and are seemingly incompetent. Mechanistically, the EJC directly conceals cryptic splicing elements by virtue of its position-specific recruitment, preventing aberrant SS definition. Unexpectedly, we discover the EJC inhibits scores of regenerated 5’ and 3’ recursive SS on segments that have already undergone splicing, and that loss of EJC regulation triggers faulty resplicing of mRNA. An important corollary is that certain intronless cDNA constructs yield unanticipated, truncated transcripts generated by resplicing. We conclude the EJC has conserved roles to defend transcriptome fidelity by (1) repressing illegitimate splice sites on pre-mRNAs, and (2) preventing inadvertent activation of such sites on spliced segments. Public Library of Science 2021-05-25 /pmc/articles/PMC8184009/ /pubmed/34033644 http://dx.doi.org/10.1371/journal.pgen.1009563 Text en © 2021 Joseph, Lai https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Joseph, Brian
Lai, Eric C.
The Exon Junction Complex and intron removal prevent re-splicing of mRNA
title The Exon Junction Complex and intron removal prevent re-splicing of mRNA
title_full The Exon Junction Complex and intron removal prevent re-splicing of mRNA
title_fullStr The Exon Junction Complex and intron removal prevent re-splicing of mRNA
title_full_unstemmed The Exon Junction Complex and intron removal prevent re-splicing of mRNA
title_short The Exon Junction Complex and intron removal prevent re-splicing of mRNA
title_sort exon junction complex and intron removal prevent re-splicing of mrna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184009/
https://www.ncbi.nlm.nih.gov/pubmed/34033644
http://dx.doi.org/10.1371/journal.pgen.1009563
work_keys_str_mv AT josephbrian theexonjunctioncomplexandintronremovalpreventresplicingofmrna
AT laiericc theexonjunctioncomplexandintronremovalpreventresplicingofmrna
AT josephbrian exonjunctioncomplexandintronremovalpreventresplicingofmrna
AT laiericc exonjunctioncomplexandintronremovalpreventresplicingofmrna