Phosphorylation-mediated regulation of alternative splicing in cancer.
Phosphorylation-mediated regulation of alternative splicing in cancer.
复制标题
磷酸化介导的癌症替代剪接的调节。
DOI：
10.1155/2013/151839
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发表时间：
2013
影响因子：
--
通讯作者：
Sette C
中科院分区：
文献类型：
--
作者：
Naro C;Sette C
选择性剪接(AS)是真核细胞基因表达调控的关键过程之一。AS催化内含子序列的去除和选定外显子的连接，从而确保初级转录本正确地加工成成熟的mRNA。AS的组合特性允许基因组编码潜力的极大扩展，因为编码不同蛋白质的多个剪接变体可能来自单个基因。剪接是由一个大的大分子复合体-剪接体介导的，剪接体的活性需要顺式作用的RNA序列元件和反式作用的RNA结合蛋白(RBP)的精细调节。核心剪接体成分和辅助剪接因子的活性都受其可逆磷酸化的调节。参与这些翻译后修饰的激酶和磷酸酶对AS的调控及其在控制真核细胞基因表达的复杂调控网络中的整合起着重要作用。在这里，我们将回顾主要的规范和非规范剪接因子激酶和磷酸酶，重点是那些与肿瘤转化的异常剪接事件有关的活性。
Alternative splicing (AS) is one of the key processes involved in the regulation of gene expression in eukaryotic cells. AS catalyzes the removal of intronic sequences and the joining of selected exons, thus ensuring the correct processing of the primary transcript into the mature mRNA. The combinatorial nature of AS allows a great expansion of the genome coding potential, as multiple splice-variants encoding for different proteins may arise from a single gene. Splicing is mediated by a large macromolecular complex, the spliceosome, whose activity needs a fine regulation exerted by cis-acting RNA sequence elements and trans-acting RNA binding proteins (RBP). The activity of both core spliceosomal components and accessory splicing factors is modulated by their reversible phosphorylation. The kinases and phosphatases involved in these posttranslational modifications significantly contribute to AS regulation and to its integration in the complex regulative network that controls gene expression in eukaryotic cells. Herein, we will review the major canonical and noncanonical splicing factor kinases and phosphatases, focusing on those whose activity has been implicated in the aberrant splicing events that characterize neoplastic transformation.