NSrp70 is a novel nuclear speckle-related protein that modulates alternative pre-mRNA splicing in vivo.
NSrp70 is a novel nuclear speckle-related protein that modulates alternative pre-mRNA splicing in vivo.
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DOI：
10.1093/nar/gkq1267
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发表时间：
2011-05
影响因子：
14.9
通讯作者：
Jun CD
中科院分区：
文献类型：
--
作者：
Kim YD;Lee JY;Oh KM;Araki M;Araki K;Yamamura K;Jun CD
核斑点是已知的mRNA剪接调节因子的存储位置。我们在这里报告了一种新的斑点蛋白NSrp70的鉴定和特性，它是基于其亚细胞定位和表观分子量。这种蛋白质最初被美国国立卫生研究院哺乳动物基因库鉴定为CCDC55，但其功能尚未确定。NSrp70与SC35和ASF/SF2以斑点状共定位并相互作用。NSrp70有一个可能的RNA识别基序、RS样区和两个卷曲的结构域，表明它在RNA加工中发挥作用。因此，以CD44、Tra2、β1和Fas为剪接报告基因，我们发现NSrp70在体内调节选择性剪接位点的选择。C末端有10个氨基酸(531-540)，包括536RD537，是一个新的核定位信号，290-471个氨基酸是斑点定位和与SC35和ASF/SF2结合的关键。N-末端(107-161)是前信使核糖核酸剪接活性所必需的。最后，我们发现小鼠的NSrp70基因敲除导致了后代的缺乏，包括胎儿胚胎。综上所述，我们证明了NSrp70是一种新的剪接调控因子，在胚胎发育的早期阶段必不可少。
Nuclear speckles are known to be the storage sites of mRNA splicing regulators. We report here the identification and characterization of a novel speckle protein, referred to as NSrp70, based on its subcellular localization and apparent molecular weight. This protein was first identified as CCDC55 by the National Institutes of Health Mammalian Gene Collection, although its function has not been assigned. NSrp70 was colocalized and physically interacted with SC35 and ASF/SF2 in speckles. NSrp70 has a putative RNA recognition motif, the RS-like region, and two coiled-coil domains, suggesting a role in RNA processing. Accordingly, using CD44, Tra2β1 and Fas constructs as splicing reporter minigenes, we found that NSrp70 modulated alternative splice site selection in vivo. The C-terminal 10 amino acids (531–540), including 536RD537, were identified as a novel nuclear localization signal, and the region spanning 290–471 amino acids was critical for speckle localization and binding to SC35 and ASF/SF2. The N-terminal region (107–161) was essential for the pre-mRNA splicing activity. Finally, we found that knockout of NSrp70 gene in mice led to a lack of progeny, including fetal embryos. Collectively, we demonstrate that NSrp70 is a novel splicing regulator and essentially required early stage of embryonic development.
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