Structural and biochemical insights into small RNA 3' end trimming by Arabidopsis SDN1.

Structural and biochemical insights into small RNA 3' end trimming by Arabidopsis SDN1.
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拟南芥 SDN1 对小 RNA 3' 末端修剪的结构和生化见解

DOI:
10.1038/s41467-018-05942-7
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发表时间:
2018-09-04
影响因子:
16.6
通讯作者:
Ma J
Ma J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen J;Liu L;You C;Gu J;Ruan W;Zhang L;Gan J;Cao C;Huang Y;Chen X;Ma J

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DEDDh 3′→5′核酸外切酶家族(小RNA降解核酸酶(SDNs))通过修剪拟南芥中ARGONAUTE 1(AGO 1)结合的microRNA的3′末端来启动其周转。在这里,我们报告了拟南芥SDN 1(残基2-300)与9个核苷酸的单链RNA底物复合的晶体结构,揭示了DEDDh结构域与N-末端结构域形成刚性相互作用,并通过其催化口袋结合RNA 3′端的4个核苷酸。结构和生化结果表明,SDN 1的C-末端结构域采用RNA识别基序(RRM)折叠,并对底物结合和SDN 1的酶促持续合成能力至关重要。此外,SDN 1在体外以RNA非依赖性方式与AGO 1 PAZ结构域相互作用,使其能够作用于AGO 1结合的microRNA。这些广泛的结构和生物化学研究可能揭示了3′→5′外切核酸酶在小的非编码RNA代谢中的常见3′末端修剪机制。小RNA降解核酸酶(SDNs)可以降解短RNA。本文报道了拟南芥SDN 1与单链RNA复合物的晶体结构,并对3′至5′核糖核酸外切酶在各种小RNA代谢中的3′末端修剪机制提供了新的见解。
A family of DEDDh 3′→5′ exonucleases known as Small RNA Degrading Nucleases (SDNs) initiates the turnover of ARGONAUTE1 (AGO1)-bound microRNAs in Arabidopsis by trimming their 3′ ends. Here, we report the crystal structure of Arabidopsis SDN1 (residues 2-300) in complex with a 9 nucleotide single-stranded RNA substrate, revealing that the DEDDh domain forms rigid interactions with the N-terminal domain and binds 4 nucleotides from the 3′ end of the RNA via its catalytic pocket. Structural and biochemical results suggest that the SDN1 C-terminal domain adopts an RNA Recognition Motif (RRM) fold and is critical for substrate binding and enzymatic processivity of SDN1. In addition, SDN1 interacts with the AGO1 PAZ domain in an RNA-independent manner in vitro, enabling it to act on AGO1-bound microRNAs. These extensive structural and biochemical studies may shed light on a common 3′ end trimming mechanism for 3′→5′ exonucleases in the metabolism of small non-coding RNAs. Small RNA degrading nucleases (SDNs) can degrade short RNAs. Here the authors report the crystal structure of Arabidopsis SDN1 in complex with a single-stranded RNA, and provide new insight into 3′ end trimming mechanism of 3′ to 5′ riboexonucleases in the metabolism of various species of small RNAs.
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