Naro Chiara, Sette Claudio
Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 Rome, Italy ; Laboratories of Neuroembryology and of Cellular and Molecular Neurobiology, Fondazione Santa Lucia IRCCS, 00143 Rome, Italy.
Int J Cell Biol. 2013;2013:151839. doi: 10.1155/2013/151839. Epub 2013 Aug 28.
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.
可变剪接（AS）是真核细胞基因表达调控中的关键过程之一。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加工成成熟mRNA。AS的组合性质使得基因组编码潜力大幅扩展，因为单个基因可能产生编码不同蛋白质的多种剪接变体。剪接由一个大型大分子复合物剪接体介导，其活性需要顺式作用RNA序列元件和反式作用RNA结合蛋白（RBP）进行精细调控。核心剪接体成分和辅助剪接因子的活性都通过其可逆磷酸化进行调节。参与这些翻译后修饰的激酶和磷酸酶对AS调控及其整合到控制真核细胞基因表达的复杂调控网络中起着重要作用。在此，我们将综述主要的经典和非经典剪接因子激酶及磷酸酶，重点关注那些其活性与肿瘤转化特征性异常剪接事件相关的激酶和磷酸酶。
