Distinct functions of the closely related tandem RNA-recognition motifs of hnRNP A1
Distinct functions of the closely related tandem RNA-recognition motifs of hnRNP A1
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DOI：
10.1017/s135583829898089x
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发表时间：
1998-09-01
期刊：
影响因子：
4.5
通讯作者：
Krainer, AR
中科院分区：
文献类型：
--
作者：
Mayeda, A;Munroe, SH;Krainer, AR
hnRNP A1通过拮抗SR蛋白调节选择性剪接。它由两个密切相关的串联RNA识别基序（RRM）组成，随后是一个富含甘氨酸的结构域。对RRM重复、缺失或交换的变异蛋白的分析表明，尽管两种RRM都是选择性剪接功能所必需的，但每种RRM起着不同的作用，它们的相对位置很重要。令人惊讶的是，RRM2而不是RRM1在复制时可以支持这种功能，尽管它们的结构非常相似。特异性RNA结合和退火对于hnRNPAl选择性剪接功能是不够的。这些观察，再加上系统发育和结构数据，表明这两个RRM是准对称的，但功能上不等价的模块，作为一个单一的二分域的组成部分演变。
hnRNP A1 regulates alternative splicing by antagonizing SR proteins. It consists of two closely related, tandem RNA-recognition motifs (RRMs), followed by a glycine-rich domain. Analysis of variant proteins with duplications, deletions, or swaps of the RRMs showed that although both RRMs ave required for alternative splicing function, each RRM plays distinct roles, and their relative position is important. Surprisingly, RRM2 but not RRM1 could support this function when duplicated, despite their very similar structure. Specific RNA binding and annealing are not sufficient for hnRNP Al alternative splicing function. These observations, together with phylogenetic and structural data, suggest that the two RRMs are quasi-symmetric but functionally nonequivalent modules that evolved as components of a single bipartite domain.