Musashi2的一个可变剪接的同工型规避了磷酸化调节作用。,Scientific Reports

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Musashi2的一个可变剪接的同工型规避了磷酸化调节作用。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Sep-14 , DOI: 10.1038/s41598-017-11917-3
Melanie C. MacNicol , Chad E. Cragle , F. Kennedy McDaniel , Linda L. Hardy , Yan Wang , Karthik Arumugam , Yasir Rahmatallah , Galina V. Glazko , Ania Wilczynska , Gwen V. Childs , Daohong Zhou , Angus M. MacNicol

Musashi RNA结合蛋白家族的作用主要是通过编码编码前分化因子和细胞周期进程抑制剂的mRNA的翻译抑制来促进干细胞自我更新并反对细胞分化。然而，在组织发育和修复过程中，必须动态调节武藏阻遏物的功能，以使细胞周期退出并分化。武藏阻遏物功能减弱的机制尚未完全建立。我们先前的工作表明，Musashi1同工型经历了位点特异性调节磷酸化。在这里，我们证明了典型的Musashi2同工型受到相似的受调控的位点特异性磷酸化，将Musashi2从阻遏物转化为目标mRNA翻译的激活物。我们还描述了另一种剪接的小说，人Musashi2（变体2）的截短同工型，它缺乏调节性磷酸化位点，并且不能促进靶mRNA的翻译。与在对抗细胞周期退出和分化中的作用一致，在许多癌症中观察到Musashi2变体2的上调，并且Musashi2变体2同工型的过表达促进了细胞转化。这些发现表明，武藏蛋白家族的可变剪接同工型具有独特的功能和调节特性，并且表明武藏同工型的差异表达可能影响细胞命运的决定。在许多癌症中观察到Musashi2变体2的上调，并且Musashi2变体2同工型的过表达促进了细胞转化。这些发现表明，武藏蛋白家族的可变剪接同工型具有独特的功能和调节特性，并且表明武藏同工型的差异表达可能影响细胞命运的决定。在许多癌症中观察到Musashi2变体2的上调，并且Musashi2变体2同工型的过表达促进了细胞转化。这些发现表明，武藏蛋白家族的可变剪接同工型具有独特的功能和调节特性，并且表明武藏同工型的差异表达可能影响细胞命运的决定。

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Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2.

The Musashi family of RNA binding proteins act to promote stem cell self-renewal and oppose cell differentiation predominantly through translational repression of mRNAs encoding pro-differentiation factors and inhibitors of cell cycle progression. During tissue development and repair however, Musashi repressor function must be dynamically regulated to allow cell cycle exit and differentiation. The mechanism by which Musashi repressor function is attenuated has not been fully established. Our prior work indicated that the Musashi1 isoform undergoes site-specific regulatory phosphorylation. Here, we demonstrate that the canonical Musashi2 isoform is subject to similar regulated site-specific phosphorylation, converting Musashi2 from a repressor to an activator of target mRNA translation. We have also characterized a novel alternatively spliced, truncated isoform of human Musashi2 (variant 2) that lacks the sites of regulatory phosphorylation and fails to promote translation of target mRNAs. Consistent with a role in opposing cell cycle exit and differentiation, upregulation of Musashi2 variant 2 was observed in a number of cancers and overexpression of the Musashi2 variant 2 isoform promoted cell transformation. These findings indicate that alternately spliced isoforms of the Musashi protein family possess distinct functional and regulatory properties and suggest that differential expression of Musashi isoforms may influence cell fate decisions.

更新日期：2017-09-14

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