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Structure of precursor microRNA's terminal loop regulates human Dicer's dicing activity by switching DExH/D domain
Protein & Cell ; (12): 185-193, 2015.
Article in English | WPRIM | ID: wpr-757606
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.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Molecular Sequence Data / Base Sequence / Chemistry / RNA Editing / Protein Structure, Tertiary / Base Pairing / MicroRNAs / Ribonuclease III / DEAD-box RNA Helicases / Genetics Limits: Humans Language: English Journal: Protein & Cell Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Molecular Sequence Data / Base Sequence / Chemistry / RNA Editing / Protein Structure, Tertiary / Base Pairing / MicroRNAs / Ribonuclease III / DEAD-box RNA Helicases / Genetics Limits: Humans Language: English Journal: Protein & Cell Year: 2015 Type: Article