hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA.

hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA.
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DOI:
10.1093/nar/gkw833
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发表时间:
2016-11-16
影响因子:
14.9
通讯作者:
Feigon J
Feigon J
中科院分区:
生物学2区
文献类型:
--
作者:
Eichhorn CD;Chug R;Feigon J

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7SK小核核糖核蛋白(snRNP)隔离并灭活正转录延伸因子B(P-TEF B),其是真核生物必需的mRNA转录因子。人镧相关蛋白7(hLARP 7)是7SK snRNP的组成部分,定位于7SK长非编码RNA的3′端。hLARP 7,特别是其C-末端结构域(CTD),对于7SK RNA稳定性和与P-TEFb的组装是必需的。hLARP 7 N端La模块结合并保护3′端免于降解,但其CTD的结构和功能作用尚不清楚。我们报告的解决方案的hLARP 7 CTD的NMR结构,并表明,这个域包含一个xRRM,一类非典型RRM首先确定在四膜虫嗜热细胞端粒酶LARP 7蛋白p65。xRRM结合在茎环4(SL 4)顶部的7SK RNA的3′端,并与未配对和碱基配对的核苷酸相互作用。这项研究证实,xRRM是一般的LARP 7家族的蛋白质,并确定了7SK RNA上的hLARP 7的结合位点,提供了深入了解功能。
The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3′ terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal La module binds and protects the 3′ end from degradation, but the structural and functional role of its CTD is unclear. We report the solution NMR structure of the hLARP7 CTD and show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3′ end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function.
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