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

被引：13

作者：

Herdt, Olga ^{[1
]}

Neumann, Alexander ^{[1
]}

Timmermann, Bernd ^{[2
]}

Heyd, Florian ^{[1
]}

机构：

[1] Free Univ Berlin, Inst Chem & Biochem, Lab RNA Biochem, D-14195 Berlin, Germany

[2] Max Planck Inst Mol Genet, Sequencing Core Facil, D-14195 Berlin, Germany

来源：

RNA | 2017年 / 23卷 / 12期

关键词：

U2AF; U2AF mutations and cancer; alternative splicing; GENE-MUTATIONS; SMALL-SUBUNIT; RNA; RECOGNITION; MACHINERY; PATHWAYS; CLONING; DESIGN; VIVO;

D O I：

10.1261/rna.061432.117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1796 / 1806

页数：11

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