The RRM1 domain of the poly(A)-binding protein from Saccharomyces cerevisiae is critical to control of mRNA deadenylation.
The RRM1 domain of the poly(A)-binding protein from Saccharomyces cerevisiae is critical to control of mRNA deadenylation.
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DOI：
10.1007/s00438-013-0759-3
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Denis CL
中科院分区：
文献类型：
--
作者：
Zhang C;Lee DJ;Chiang YC;Richardson R;Park S;Wang X;Laue TM;Denis CL
来自酵母的聚(A)结合蛋白PAB1在控制mRNA死基化率中起重要作用。其RRM1或富含脯氨酸结构域（P结构域）的缺失严重限制了死蛋白化并减缓了mRNA的降解。由于这些大的缺失可能对PAB1的结构有未知的影响，因此使用了不同的策略来确定RRM1和P结构域对死基化的重要性。由于P结构域的大小和序列在真核生物中有很大的差异，因此我们将两个人类PABPCs和爪蟾的P结构域替换为PAB1的P结构域。然而，与PAB1相比，得到的PAB1杂交蛋白在mRNA死基化方面表现出有限或没有差异。与P结构域相比，RRM1结构域在物种间是高度保守的，研究人员对RRM1结构域进行了系统诱变，以确定其功能区域。RRM1的RNA结合表面的一些突变抑制了死烯化，而其外部非RNA结合表面的一组突变将死烯化从缓慢的分布过程转变为快速的过程性死烯化。这些结果表明，RRM1结构域是PAB1中控制死基化的更关键的区域，它至少由两个可区分的功能区组成。
The poly(A)-binding protein PAB1 from the yeast Saccharomyces cerevisiae plays an important role in controlling mRNA deadenylation rates. Deletion of either its RRM1 or proline-rich domain (P domain) severely restricts deadenylation and slows mRNA degradation. Because these large deletions could be having unknown effects on the structure of PAB1, different strategies were used to determine the importance of the RRM1 and P domains to deadenylation. Since the P domain is quite variable in size and sequence among eukaryotes, P domains from two human PABPCs and from Xenopus were substituted for that of PAB1. The resultant PAB1 hybrid proteins, however, displayed limited or no difference in mRNA deadenylation as compared to PAB1. In contrast to the P domain, the RRM1 domain is highly conserved across species, and a systematic mutagenesis of the RRM1 domain was undertaken to identify its functional regions. Several mutations along the RNA binding surface of RRM1 inhibited deadenylation whereas one set of mutations on its exterior non-RNA binding surface shifted deadenylation from a slow distributive process to a rapid processive deadenylation. These results suggest that the RRM1 domain is the more critical region of PAB1 for controlling deadenylation and consists of at least two distinguishable functional regions.
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