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

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 specie...

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Autores principales: Liu, Zhongmin, Wang, Jia, Li, Gang, Wang, Hong-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Higher Education Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348242/
https://www.ncbi.nlm.nih.gov/pubmed/25549615
http://dx.doi.org/10.1007/s13238-014-0124-2
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author Liu, Zhongmin
Wang, Jia
Li, Gang
Wang, Hong-Wei
author_facet Liu, Zhongmin
Wang, Jia
Li, Gang
Wang, Hong-Wei
author_sort Liu, Zhongmin
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-014-0124-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-43482422015-03-05 Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain Liu, Zhongmin Wang, Jia Li, Gang Wang, Hong-Wei Protein Cell Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-014-0124-2) contains supplementary material, which is available to authorized users. Higher Education Press 2014-12-31 2015-03 /pmc/articles/PMC4348242/ /pubmed/25549615 http://dx.doi.org/10.1007/s13238-014-0124-2 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Research Article
Liu, Zhongmin
Wang, Jia
Li, Gang
Wang, Hong-Wei
Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain
title Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain
title_full Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain
title_fullStr Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain
title_full_unstemmed Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain
title_short Structure of precursor microRNA’s terminal loop regulates human Dicer’s dicing activity by switching DExH/D domain
title_sort structure of precursor microrna’s terminal loop regulates human dicer’s dicing activity by switching dexh/d domain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348242/
https://www.ncbi.nlm.nih.gov/pubmed/25549615
http://dx.doi.org/10.1007/s13238-014-0124-2
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