Structure of precursor microRNA's terminal loop regulates human Dicer's dicing activity by switching DExH/D domain.
10.1007/s13238-014-0124-2
- Author:
Zhongmin LIU
1
;
Jia WANG
;
Gang LI
;
Hong-Wei WANG
Author Information
1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
- Publication Type:Journal Article
- MeSH:
Base Pairing;
Base Sequence;
DEAD-box RNA Helicases;
chemistry;
genetics;
Humans;
MicroRNAs;
chemistry;
genetics;
Molecular Conformation;
Molecular Sequence Data;
Protein Structure, Tertiary;
RNA Editing;
genetics;
Ribonuclease III;
chemistry;
genetics
- From:
Protein & Cell
2015;6(3):185-193
- CountryChina
- Language:English
-
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 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.
