Misregulation of pre-mRNA alternative splicing in cancer.
Misregulation of pre-mRNA alternative splicing in cancer.
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DOI：
10.1158/2159-8290.cd-13-0253
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发表时间：
2013-11
期刊：
影响因子：
28.2
通讯作者：
Manley JL
中科院分区：
文献类型：
--
作者：
Zhang J;Manley JL
MRNA前体的选择性剪接使一个基因能够产生多种不同功能的蛋白质亚型。在正常情况下，这一机制受到严格调控，以便人类基因组产生足以满足复杂组织功能要求的蛋白质组多样性。然而，当解除调控时，癌细胞利用这一机制产生具有增加、缺失或改变的功能域的异常蛋白，这些功能域有助于肿瘤的发生。在这里，我们讨论了癌症中选择性剪接错误调控的各个方面，重点讨论了剪接事件受调控剪接因子放松的影响，以及最近识别剪接机制突变成分的研究。
Alternative splicing of mRNA precursors enables one gene to produce multiple protein isoforms with differing functions. Under normal conditions, this mechanism is tightly regulated in order for the human genome to generate proteomic diversity sufficient for the functional requirements of complex tissues. When deregulated, however, cancer cells take advantage of this mechanism to produce aberrant proteins with added, deleted, or altered functional domains that contribute to tumorigenesis. Here we discuss aspects of alternative splicing misregulation in cancer, focusing on splicing events affected by deregulation of regulatory splicing factors and also recent studies identifying mutated components of the splicing machinery.