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The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients

Recent work has identified cancer-associated U2AF35 missense mutations in two zinc-finger (ZnF) domains, but little is known about Q157R/P substitutions within the second ZnF. Surprisingly, we find that the c.470A>G mutation not only leads to the Q157R substitution, but also creates an alternativ...

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Detalles Bibliográficos
Autores principales: Herdt, Olga, Neumann, Alexander, Timmermann, Bernd, Heyd, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689001/
https://www.ncbi.nlm.nih.gov/pubmed/28893951
http://dx.doi.org/10.1261/rna.061432.117
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author Herdt, Olga
Neumann, Alexander
Timmermann, Bernd
Heyd, Florian
author_facet Herdt, Olga
Neumann, Alexander
Timmermann, Bernd
Heyd, Florian
author_sort Herdt, Olga
collection PubMed
description Recent work has identified cancer-associated U2AF35 missense mutations in two zinc-finger (ZnF) domains, but little is known about Q157R/P substitutions within the second ZnF. Surprisingly, we find that the c.470A>G mutation not only leads to the Q157R substitution, but also creates an alternative 5′ splice site (ss) resulting in the deletion of four amino acids (Q157Rdel). Q157P, Q157R, and Q157Rdel control alternative splicing of distinct groups of exons in cell culture and in human patients, suggesting that missplicing of different targets may contribute to cellular aberrations. Our data emphasize the importance to explore missense mutations beyond altered protein sequence.
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spelling pubmed-56890012018-12-01 The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients Herdt, Olga Neumann, Alexander Timmermann, Bernd Heyd, Florian RNA Report Recent work has identified cancer-associated U2AF35 missense mutations in two zinc-finger (ZnF) domains, but little is known about Q157R/P substitutions within the second ZnF. Surprisingly, we find that the c.470A>G mutation not only leads to the Q157R substitution, but also creates an alternative 5′ splice site (ss) resulting in the deletion of four amino acids (Q157Rdel). Q157P, Q157R, and Q157Rdel control alternative splicing of distinct groups of exons in cell culture and in human patients, suggesting that missplicing of different targets may contribute to cellular aberrations. Our data emphasize the importance to explore missense mutations beyond altered protein sequence. Cold Spring Harbor Laboratory Press 2017-12 /pmc/articles/PMC5689001/ /pubmed/28893951 http://dx.doi.org/10.1261/rna.061432.117 Text en © 2017 Herdt et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Report
Herdt, Olga
Neumann, Alexander
Timmermann, Bernd
Heyd, Florian
The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients
title The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients
title_full The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients
title_fullStr The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients
title_full_unstemmed The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients
title_short The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in Q157R patients
title_sort cancer-associated u2af35 470a>g (q157r) mutation creates an in-frame alternative 5′ splice site that impacts splicing regulation in q157r patients
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689001/
https://www.ncbi.nlm.nih.gov/pubmed/28893951
http://dx.doi.org/10.1261/rna.061432.117
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