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学科主题: 基础医学
题名:
Structure of precursor microRNA′s terminal loop regulates human Dicer′s dicing activity by switching DExH/D domain
作者: Liu, Zhongmin1,2; Wang, Jia2; Li, Gang1; Wang, Hong-Wei2
关键词: human Dicer ; DExH/D (ATPase-helicase) domain ; pre-miRNA-151 ; A-to-I editing ; single particle electron microscopy
刊名: PROTEIN & CELL
发表日期: 2015-03-01
DOI: 10.1007/s13238-014-0124-2
卷: 6, 期:3, 页:185-193
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: RISC-LOADING COMPLEX ; ADAR DEAMINASES ; RNA ; MIRNAS ; URIDYLATION ; BIOGENESIS ; MECHANISMS ; CLEAVAGE
英文摘要:

Almost all pre-miRNAs in eukaryotic cytoplasm are recognized and processed into double-stranded microRNAs by the endonuclease Dicer protein comprising of multiple domains. As a key player in the small RNA induced gene silencing pathway, the major domains of Dicer are conserved among different species with the exception of the N-terminal components. Human Dicer′s N-terminal domain has been shown to play an auto-inhibitory function of the protein′s dicing activity. Such an auto-inhibition can be released when the human Dicer protein dimerizes with its partner protein, such as TRBP, PACT through the N-terminal DExH/D (ATPase-helicase) domain. The typical feature of a pre-miRNA contains a terminal loop and a stem duplex, which bind to human Dicer′s DExH/D (ATPase-helicase) domain and PAZ domain respectively during the dicing reaction. Here, we show that pre-miRNA′s terminal loop can regulate human Dicer′s enzymatic activity by interacting with the DExH/D (ATPase-helicase) domain. We found that various editing products of pre-miR-151 by the ADAR1P110 protein, an A-to-I editing enzyme that modifies pre-miRNAs sequence, have different terminal loop structures and different activity regulatory effects on human Dicer. Single particle electron microscopy reconstruction revealed that pre-miRNAs with different terminal loop structures induce human Dicer′s DExH/D (ATPase-helicase) domain into different conformational states, in correlation with their activity regulatory effects.

语种: 英语
所属项目编号: 31270765 ; 2010CB912401
项目资助者: National Natural Science Foundation of China ; National Basic Research Program (973 Program)
WOS记录号: WOS:000350668100004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64966
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
2.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China

Recommended Citation:
Liu, Zhongmin,Wang, Jia,Li, Gang,et al. Structure of precursor microRNA′s terminal loop regulates human Dicer′s dicing activity by switching DExH/D domain[J]. PROTEIN & CELL,2015,6(3):185-193.
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