Frameshift indels introduced by genome editing can lead to in-frame exon skipping.
The introduction of frameshift indels by genome editing has emerged as a powerful technique to study the functions of uncharacterized genes in cell lines and model organisms. Such mutations should lead to mRNA degradation owing to nonsense-mediated mRNA decay or the production of severely truncated...
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doaj-1a33658a753544a1839021af69869ef62020-11-25T01:35:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017870010.1371/journal.pone.0178700Frameshift indels introduced by genome editing can lead to in-frame exon skipping.Simon LalondeOliver A StoneSamuel LessardAdam LavertuJessica DesjardinsMélissa BeaudoinManuel RivasDidier Y R StainierGuillaume LettreThe introduction of frameshift indels by genome editing has emerged as a powerful technique to study the functions of uncharacterized genes in cell lines and model organisms. Such mutations should lead to mRNA degradation owing to nonsense-mediated mRNA decay or the production of severely truncated proteins. Here, we show that frameshift indels engineered by genome editing can also lead to skipping of "multiple of three nucleotides" exons. Such splicing events result in in-frame mRNA that may encode fully or partially functional proteins. We also characterize a segregating nonsense variant (rs2273865) located in a "multiple of three nucleotides" exon of LGALS8 that increases exon skipping in human erythroblast samples. Our results highlight the potentially frequent contribution of exonic splicing regulatory elements and are important for the interpretation of negative results in genome editing experiments. Moreover, they may contribute to a better annotation of loss-of-function mutations in the human genome.http://europepmc.org/articles/PMC5453576?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Simon Lalonde Oliver A Stone Samuel Lessard Adam Lavertu Jessica Desjardins Mélissa Beaudoin Manuel Rivas Didier Y R Stainier Guillaume Lettre |
spellingShingle |
Simon Lalonde Oliver A Stone Samuel Lessard Adam Lavertu Jessica Desjardins Mélissa Beaudoin Manuel Rivas Didier Y R Stainier Guillaume Lettre Frameshift indels introduced by genome editing can lead to in-frame exon skipping. PLoS ONE |
author_facet |
Simon Lalonde Oliver A Stone Samuel Lessard Adam Lavertu Jessica Desjardins Mélissa Beaudoin Manuel Rivas Didier Y R Stainier Guillaume Lettre |
author_sort |
Simon Lalonde |
title |
Frameshift indels introduced by genome editing can lead to in-frame exon skipping. |
title_short |
Frameshift indels introduced by genome editing can lead to in-frame exon skipping. |
title_full |
Frameshift indels introduced by genome editing can lead to in-frame exon skipping. |
title_fullStr |
Frameshift indels introduced by genome editing can lead to in-frame exon skipping. |
title_full_unstemmed |
Frameshift indels introduced by genome editing can lead to in-frame exon skipping. |
title_sort |
frameshift indels introduced by genome editing can lead to in-frame exon skipping. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
The introduction of frameshift indels by genome editing has emerged as a powerful technique to study the functions of uncharacterized genes in cell lines and model organisms. Such mutations should lead to mRNA degradation owing to nonsense-mediated mRNA decay or the production of severely truncated proteins. Here, we show that frameshift indels engineered by genome editing can also lead to skipping of "multiple of three nucleotides" exons. Such splicing events result in in-frame mRNA that may encode fully or partially functional proteins. We also characterize a segregating nonsense variant (rs2273865) located in a "multiple of three nucleotides" exon of LGALS8 that increases exon skipping in human erythroblast samples. Our results highlight the potentially frequent contribution of exonic splicing regulatory elements and are important for the interpretation of negative results in genome editing experiments. Moreover, they may contribute to a better annotation of loss-of-function mutations in the human genome. |
url |
http://europepmc.org/articles/PMC5453576?pdf=render |
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