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 En
| WPRIM
| ID: wpr-757606
Responsible library:
WPRO
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.
Full text:
1
Index:
WPRIM
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:
En
Journal:
Protein & Cell
Year:
2015
Type:
Article