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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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 |
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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 |
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