Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer.
Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer.
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DOI：
10.1158/1541-7786.mcr-14-0131
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Krainer AR
中科院分区：
文献类型：
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作者：
Das S;Krainer AR
丝氨酸/精氨酸剪接因子1（Serine/Arginine Splicing Factor 1，SRSF1）是剪接调节因子SR蛋白家族的原型成员。自二十多年前被发现以来，SRSF1通过其调节的大量复杂生物学途径一再令人惊讶和有趣的研究人员。这些包括mRNA代谢的几个关键方面，如mRNA剪接，稳定性和翻译，以及其他mRNA非依赖性过程，如miRNA（miR）加工，蛋白质类小泛素化和核仁应激反应。在这篇综述中，SRSF1的结构特征进行了讨论，因为它们涉及到复杂的剪接机制和它执行的功能的多样性。类似地，提供了相关可变剪接转录物和SRSF1相互作用蛋白的列表。最后，强调SRSF1原癌基因在人类癌症中过度表达的有害后果，以及SRSF1介导的转化的复杂机制和途径。关于SRSF1的累积知识为它在维持细胞稳态中所起的整体作用提供了关键的见解，并为抗癌治疗提供了新的靶点。
Serine/Arginine Splicing Factor 1 (SRSF1) is the archetype member of the SR protein family of splicing regulators. Since its discovery, over two decades ago, SRSF1 has been repeatedly surprising and intriguing investigators by the plethora of complex biological pathways it regulates. These include several key aspects of mRNA metabolism, such as mRNA splicing, stability, and translation, as well as other mRNA-independent processes, such as miRNA (miR) processing, protein sumoylation, and the nucleolar-stress response. In this review, the structural features of SRSF1 are discussed as they relate to the intricate mechanism of splicing and the multiplicity of functions it performs. Similarly, a list of relevant alternatively spliced transcripts and SRSF1 interacting proteins is provided. Finally, emphasis is given to the deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers, and the complex mechanisms and pathways underlying SRSF1-mediated transformation. The accumulated knowledge about SRSF1 provides critical insight into the integral role it plays in maintaining cellular homeostasis, and suggests new targets for anti-cancer therapy.