Dephosphorylation-dependent sorting of SR splicing factors during mRNP maturation
Dephosphorylation-dependent sorting of SR splicing factors during mRNP maturation
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DOI：
10.1016/j.molcel.2005.09.015
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发表时间：
2005-11-11
期刊：
影响因子：
16
通讯作者：
Fu, XD
中科院分区：
文献类型：
--
作者：
Lin, SR;Xiao, R;Fu, XD
SR蛋白是序列特异性RNA结合蛋白家族，最初被发现是前体mRNA剪接的必需因子，最近涉及mRNA转运、稳定性和翻译。在这里，我们使用了来自条件性基因敲除小鼠的遗传互补系统，以解决SR蛋白在体内的功能和调节。我们证明，ASF/SF 2和SC 35都是细胞活力所需的，但令人惊讶的是，ASF/SF 2的效应RS结构域是MEFs中细胞存活所必需的。尽管穿梭SR蛋白与mRNA输出有关，但防止ASF/SF 2穿梭对mRNA输出的影响很小。我们发现，穿梭和nonshuttling SR蛋白在mRNP成熟过程中以有序的方式分离，表明不同SR蛋白的不同回收途径。我们进一步表明，这一过程是由RS结构域的差异去磷酸化调节的，从而揭示了mRNP从剪接到输出过渡的分选机制。
SR proteins are a family of sequence-specific RNA binding proteins originally discovered as essential factors for pre-mRNA splicing and recently implicated in mRNA transport, stability, and translation. Here, we used a genetic complementation system derived from conditional knockout mice to address the function and regulation of SR proteins in vivo. We demonstrate that ASF/SF2 and SC35 are each required for cell viability, but, surprisingly, the effector RS domain of ASF/SF2 is dispensable for cell survival in MEFs. Although shuttling SR proteins have been implicated in mRNA export, prevention of ASF/SF2 from shuttling had little impact on mRNA export. We found that shuttling and nonshuttling SR proteins are segregated in an orderly fashion during mRNP maturation, indicating distinct recycling pathways for different SR proteins. We further showed that this process is regulated by differential dephosphorylation of the RS domain, thus revealing a sorting mechanism for mRNP transition from splicing to export.