Musashi1 Cooperates in Abnormal Cell Lineage Protein 28 (Lin28)-mediated Let-7 Family MicroRNA Biogenesis in Early Neural Differentiation
Musashi1 Cooperates in Abnormal Cell Lineage Protein 28 (Lin28)-mediated Let-7 Family MicroRNA Biogenesis in Early Neural Differentiation
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DOI：
10.1074/jbc.m110.199166
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发表时间：
2011-05-06
影响因子：
4.8
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
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作者：
Kawahara, Hironori;Okada, Yohei;Okano, Hideyuki
Musashi 1（Msi 1）是一种RNA结合蛋白，在神经干/祖细胞（NS/PC）以及其他组织干细胞中高度表达。Msi 1与NS/PC中其靶mRNA的3 '-UTR结合，阻止其翻译，并干扰NS/PC分化。我们以前的研究表明，Msi 1与eIF 4G竞争结合poly（A）结合蛋白，并抑制80 S核糖体的组装。在这里，我们表明Msi 1与Lin 28协同工作，以调节在细胞核中发生的裁剪步骤中的转录后microRNA（miRNA）生物合成。已知Lin 28及其结合伴侣末端尿苷酰转移酶4（TUT 4）通过在切割步骤阻断let-7 miRNA生物发生来维持胚胎干细胞多能性。有趣的是，我们发现在胚胎干细胞的早期神经分化过程中，Msi 1增强了Lin 28在细胞核中的定位，并且还抑制了另一个let-7家族miRNA miR 98的核裁剪步骤。这些结果表明，Msi 1可以通过控制参与miRNA生物合成的蛋白质的亚细胞定位以及调节其靶mRNA的翻译来影响干细胞的维持和分化。
Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem/progenitor cells (NS/PCs) as well as in other tissue stem cells. Msi1 binds to the 3'-UTR of its target mRNAs in NS/PCs, prevents their translation, and interferes with NS/PC differentiation. We previously showed that Msi1 competes with eIF4G to bind poly(A)-binding protein and inhibits assembly of the 80 S ribosome. Here we show that Msi1 works in concert with Lin28 to regulate post-transcriptional microRNA (miRNA) biogenesis in the cropping step, which occurs in the nucleus. Lin28 and its binding partner terminal uridylyltransferase 4 (TUT4) are known to maintain embryonic stem cell pluripotency by blocking let-7 miRNA biogenesis at the dicing step. Interestingly, we found that during early neural differentiation of embryonic stem cells, Msi1 enhanced the localization of Lin28 to the nucleus and also inhibited the nuclear cropping step of another let-7 family miRNA, miR98. These results suggest that Msi1 can influence stem cell maintenance and differentiation by controlling the subcellular localization of proteins involved in miRNA biogenesis, as well as by regulating the translation of its target mRNA.