Prevalent RNA recognition motif duplication in the human genome.
Prevalent RNA recognition motif duplication in the human genome.
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DOI：
10.1261/rna.044081.113
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Tsai YS;Gomez SM;Wang Z
本文分析了单个RNA结合蛋白中多个RNA识别基序（RRM）的起源。一个主要的发现是，这样的RRM（同胞RRM）有显着更高的相似性比预期的机会。这些结果表明，兄弟RRM出现通过域重复。蛋白质对RNA的序列特异性识别是通过各种RNA结合结构域介导的，其中RNA识别基序（RRM）是最常见的，并且存在于> 50%的RNA结合蛋白（RBP）中。许多RBP含有多个RRM，目前还不清楚每个RRM如何有助于整个蛋白质的结合特异性。我们发现相同RBP内的RRM（即，同胞RRM）倾向于具有比偶然预期的显著更高的相似性。来自多个物种共享的RBP的同胞RRM对往往具有比仅在单个物种中发现的那些更低的相似性，这表明同一蛋白质内的多个RRM可能来自结构域重复，然后通过随机突变而发散。这一发现的例证是最近的RRM结构域重复DAZ蛋白和古老的重复PABP蛋白。此外，我们发现兄弟RRM之间的不同相似性与RBP的不同功能相关，并且RBP倾向于包含低复杂性的重复序列。总之，这项研究表明，在哺乳动物中，具有多个RRM的RBP的数量已经扩大，并且多个兄弟RRM可以以合作的方式识别相似的靶基序。
This paper provides an analysis of the origin of multiple RNA recognition motifs (RRMs) within single RNA-binding proteins. One main finding is that such RRMs (sibling RRMs) have significantly higher similarity than expected by chance. These results suggest that sibling RRMs arose through domain duplication. The sequence-specific recognition of RNA by proteins is mediated through various RNA binding domains, with the RNA recognition motif (RRM) being the most frequent and present in >50% of RNA-binding proteins (RBPs). Many RBPs contain multiple RRMs, and it is unclear how each RRM contributes to the binding specificity of the entire protein. We found that RRMs within the same RBP (i.e., sibling RRMs) tend to have significantly higher similarity than expected by chance. Sibling RRM pairs from RBPs shared by multiple species tend to have lower similarity than those found only in a single species, suggesting that multiple RRMs within the same protein might arise from domain duplication followed by divergence through random mutations. This finding is exemplified by a recent RRM domain duplication in DAZ proteins and an ancient duplication in PABP proteins. Additionally, we found that different similarities between sibling RRMs are associated with distinct functions of an RBP and that the RBPs tend to contain repetitive sequences with low complexity. Taken together, this study suggests that the number of RBPs with multiple RRMs has expanded in mammals and that the multiple sibling RRMs may recognize similar target motifs in a cooperative manner.
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