RESEARCH ARTICLE

Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain

  • Zhongmin Liu 1,2 ,
  • Jia Wang 2 ,
  • Gang Li , 1 ,
  • Hong-Wei Wang , 2
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  • 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
  • 2. Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China

Received date: 18 Oct 2014

Accepted date: 13 Nov 2014

Published date: 01 Apr 2015

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 autoinhibitory 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.

Cite this article

Zhongmin Liu , Jia Wang , Gang Li , Hong-Wei Wang . 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 . DOI: 10.1007/s13238-014-0124-2

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