Structural and functional insights into human Tudor-SN, a key component linking RNA interference and editing.

Structural and functional insights into human Tudor-SN, a key component linking RNA interference and editing.
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DOI:
10.1093/nar/gkn236
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发表时间:
2008-06
影响因子:
14.9
通讯作者:
Yuan HS
Yuan HS
中科院分区:
生物学2区
文献类型:
--
作者:
Li CL;Yang WZ;Chen YP;Yuan HS

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人Tudor-SN参与降解超编辑的含肌苷的microRNA前体,从而连接RNA干扰和编辑的途径。Tudor-SN含有葡萄球菌核酸酶样结构域的四个串联重复序列(SN 1-SN 4),随后是Tudor和C-末端SN结构域(SN 5)。在这里,我们表明Tudor-SN需要SN结构域的串联重复才能实现其RNA结合和切割活性。64-kD截短形式的人Tudor-SN的晶体结构进一步显示四个结构域SN 3、SN 4、tudor和SN 5组装成新月形结构。由SN 3和SN 4结构域共同形成的凹碱性表面可能参与RNA结合,其中柠檬酸根离子结合在推定的RNA酶活性位点。额外的建模研究为Tudor-SN优先切割含有多个I·U摆动配对序列的RNA提供了结构基础。总的来说,这些结果表明Tudor-SN中SN结构域的串联重复序列作为捕获RNA底物的钳起作用。
Human Tudor-SN is involved in the degradation of hyper-edited inosine-containing microRNA precursors, thus linking the pathways of RNA interference and editing. Tudor-SN contains four tandem repeats of staphylococcal nuclease-like domains (SN1–SN4) followed by a tudor and C-terminal SN domain (SN5). Here, we showed that Tudor-SN requires tandem repeats of SN domains for its RNA binding and cleavage activity. The crystal structure of a 64-kD truncated form of human Tudor-SN further shows that the four domains, SN3, SN4, tudor and SN5, assemble into a crescent-shaped structure. A concave basic surface formed jointly by SN3 and SN4 domains is likely involved in RNA binding, where citrate ions are bound at the putative RNase active sites. Additional modeling studies provide a structural basis for Tudor-SN's preference in cleaving RNA containing multiple I·U wobble-paired sequences. Collectively, these results suggest that tandem repeats of SN domains in Tudor-SN function as a clamp to capture RNA substrates.
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