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Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1

The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplasti...

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Autores principales: Yoshida, Hisashi, Park, Sam-Yong, Sakashita, Gyosuke, Nariai, Yuko, Kuwasako, Kanako, Muto, Yutaka, Urano, Takeshi, Obayashi, Eiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505975/
https://www.ncbi.nlm.nih.gov/pubmed/32958768
http://dx.doi.org/10.1038/s41467-020-18559-6
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author Yoshida, Hisashi
Park, Sam-Yong
Sakashita, Gyosuke
Nariai, Yuko
Kuwasako, Kanako
Muto, Yutaka
Urano, Takeshi
Obayashi, Eiji
author_facet Yoshida, Hisashi
Park, Sam-Yong
Sakashita, Gyosuke
Nariai, Yuko
Kuwasako, Kanako
Muto, Yutaka
Urano, Takeshi
Obayashi, Eiji
author_sort Yoshida, Hisashi
collection PubMed
description The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplastic syndromes. Here, we describe the first crystal structures of wild-type and pathogenic mutant U2AF1 complexed with target RNA, revealing the mechanism of 3´ splice site selection, and how aberrant splicing results from clinically important mutations. Unexpected features of this mechanism may assist the future development of new treatments against diseases caused by splicing errors.
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spelling pubmed-75059752020-10-05 Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1 Yoshida, Hisashi Park, Sam-Yong Sakashita, Gyosuke Nariai, Yuko Kuwasako, Kanako Muto, Yutaka Urano, Takeshi Obayashi, Eiji Nat Commun Article The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplastic syndromes. Here, we describe the first crystal structures of wild-type and pathogenic mutant U2AF1 complexed with target RNA, revealing the mechanism of 3´ splice site selection, and how aberrant splicing results from clinically important mutations. Unexpected features of this mechanism may assist the future development of new treatments against diseases caused by splicing errors. Nature Publishing Group UK 2020-09-21 /pmc/articles/PMC7505975/ /pubmed/32958768 http://dx.doi.org/10.1038/s41467-020-18559-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yoshida, Hisashi
Park, Sam-Yong
Sakashita, Gyosuke
Nariai, Yuko
Kuwasako, Kanako
Muto, Yutaka
Urano, Takeshi
Obayashi, Eiji
Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1
title Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1
title_full Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1
title_fullStr Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1
title_full_unstemmed Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1
title_short Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1
title_sort elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the u2af1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505975/
https://www.ncbi.nlm.nih.gov/pubmed/32958768
http://dx.doi.org/10.1038/s41467-020-18559-6
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