编码 RNA 剪接机制成分的基因的体细胞突变经常发生在多种形式的癌症中。癌症中最常见的突变 RNA 剪接因子影响内含子分支位点和 3' 剪接位点识别。这些包括核心 RNA 剪接因子 SF3B1 中的突变以及 U2AF1/2 异二聚体复合物中的突变，该复合物将 SF3b 复合物募集到 3' 剪接位点。此外，剪接调节蛋白 SRSF2 和 RBM10 的突变在癌症中很常见，最近有研究表明，小核 RNA (snRNA) 的变异形式可能会导致癌症中的剪接失调。在这里，我们描述了这些因子的突变改变剪接位点识别的分子机制，以及对该过程的研究如何对癌症发病机制和剪接的分子调控产生新的见解。我们还讨论了将突变 RNA 剪接因子与剪接之外的 RNA 代谢联系起来的数据。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Somatic mutations in genes encoding components of the RNA splicing machinery occur frequently in multiple forms of cancer. The most frequently mutated RNA splicing factors in cancer impact intronic branch site and 3' splice site recognition. These include mutations in the core RNA splicing factor SF3B1 as well as mutations in the U2AF1/2 heterodimeric complex, which recruits the SF3b complex to the 3' splice site. Additionally, mutations in splicing regulatory proteins SRSF2 and RBM10 are frequent in cancer, and there has been a recent suggestion that variant forms of small nuclear RNAs (snRNAs) may contribute to splicing dysregulation in cancer. Here, we describe molecular mechanisms by which mutations in these factors alter splice site recognition and how studies of this process have yielded new insights into cancer pathogenesis and the molecular regulation of splicing. We also discuss data linking mutant RNA splicing factors to RNA metabolism beyond splicing.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.