Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions.
Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions.
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DOI：
10.1093/nar/gkr1139
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发表时间：
2012-04
影响因子：
14.9
通讯作者：
Katahira M
中科院分区：
文献类型：
--
作者：
Ohyama T;Nagata T;Tsuda K;Kobayashi N;Imai T;Okano H;Yamazaki T;Katahira M
哺乳动物Musashi 1（Msi 1）是一种RNA结合蛋白，调节靶mRNA的翻译，并参与细胞“干性”和肿瘤发生的维持。据报道，Msi 1与编码Notch抑制剂的Numb mRNA的3′-非翻译区结合，并通过与eIF 4G竞争PABP结合来阻碍其翻译的起始，从而触发Notch信号传导。在此，Msi 1利用其核糖核蛋白（RNP）型RNA结合结构域（RBD）、RBD 1和RBD 2识别靶RNA序列的机制已通过鉴定每个RBD的最小结合RNA和确定RBD 1：RNA复合物的三维结构而被揭示。发现Msi 1 RBD 1识别靶序列的独特相互作用：腺嘌呤被两个苯丙氨酸夹在中间，鸟嘌呤堆叠在β1和α1之间环中的色氨酸上。我们为Msi 1 RBD 1和RBD 2定义的最小识别序列实际上已经在迄今报道的许多Msi 1靶mRNA中发现。本研究为理解Musashi家族蛋白的生物学特性提供了分子线索。
Mammalian Musashi1 (Msi1) is an RNA-binding protein that regulates the translation of target mRNAs, and participates in the maintenance of cell ‘stemness’ and tumorigenesis. Msi1 reportedly binds to the 3′-untranslated region of mRNA of Numb, which encodes Notch inhibitor, and impedes initiation of its translation by competing with eIF4G for PABP binding, resulting in triggering of Notch signaling. Here, the mechanism by which Msi1 recognizes the target RNA sequence using its Ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), RBD1 and RBD2 has been revealed on identification of the minimal binding RNA for each RBD and determination of the three-dimensional structure of the RBD1:RNA complex. Unique interactions were found for the recognition of the target sequence by Msi1 RBD1: adenine is sandwiched by two phenylalanines and guanine is stacked on the tryptophan in the loop between β1 and α1. The minimal recognition sequences that we have defined for Msi1 RBD1 and RBD2 have actually been found in many Msi1 target mRNAs reported to date. The present study provides molecular clues for understanding the biology involving Musashi family proteins.
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