Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors.

Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors.
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DOI:
10.1038/nature13284
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发表时间:
2014-07-03
期刊:
影响因子:
64.8
通讯作者:
Martinez J
Martinez J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Popow J;Jurkin J;Schleiffer A;Martinez J

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RNA连接酶在真核生物、古细菌和细菌的许多细胞过程中发挥着重要作用,包括RNA修复和应激诱导的信使RNA剪接。在古细菌和真核生物中,RNA连接酶也在转移RNA剪接中发挥作用,以产生蛋白质合成所需的功能性trna。我们最近发现了人类tRNA剪接连接酶,这是一种以RTCB(也称为HSPC117, C22orf28, FAAP和D10Wsu52e)为基本亚基的多聚体蛋白复合物。额外的复杂成分ASW(也称为C2orf49)、CGI-99(也称为C14orf166)、FAM98B和DEAD-box解旋酶DDX1在RNA连接中的功能尚不清楚。利用真核生物同源基团簇的优势,我们发现了一种功能未知的蛋白质——古酶(ARCH,也被称为ZBTB8OS),它是人类tRNA连接酶复合体充分发挥活性所必需的,并且与DDX1合作,促进了rtcb -鸟苷酸中间产物的形成,对哺乳动物RNA连接至关重要。我们的研究结果确定了DDX1在人类tRNA连接酶复合体中的作用,并表明太古酶和RtcB蛋白的广泛共存意味着它们的功能相互作用的进化保护。
RNA ligases have essential roles in many cellular processes in eukaryotes, archaea and bacteria, including in RNA repair,and stress-induced splicing of messenger RNA. In archaea and eukaryotes, RNA ligases also have a role in transfer RNA splicing to generate functional tRNAs required for protein synthesis,,,. We recently identified the human tRNA splicing ligase, a multimeric protein complex with RTCB (also known as HSPC117, C22orf28, FAAP and D10Wsu52e) as the essential subunit. The functions of the additional complex components ASW (also known as C2orf49), CGI-99 (also known as C14orf166), FAM98B and the DEAD-box helicase DDX1 in the context of RNA ligation have remained unclear. Taking advantage of clusters of eukaryotic orthologous groups, here we find that archease (ARCH; also known as ZBTB8OS), a protein of unknown function, is required for full activity of the human tRNA ligase complex and, in cooperation with DDX1, facilitates the formation of an RTCB–guanylate intermediate central to mammalian RNA ligation. Our findings define a role for DDX1 in the context of the human tRNA ligase complex and suggest that the widespread co-occurrence of archease and RtcB proteins implies evolutionary conservation of their functional interplay.
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