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Protein Cell. 2015 Mar;6(3):185-93. doi: 10.1007/s13238-014-0124-2. Epub 2014 Dec 31.

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

Author information

1
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

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.

PMID:
25549615
PMCID:
PMC4348242
DOI:
10.1007/s13238-014-0124-2
[Indexed for MEDLINE]
Free PMC Article

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