Structural and functional basis of mammalian microRNA biogenesis by Dicer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00567393" target="_blank" >RIV/68378050:_____/22:00567393 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/22:00128561

Výsledek na webu

<a href="https://doi.org/10.1016/j.molcel.2022.10.010" target="_blank" >https://doi.org/10.1016/j.molcel.2022.10.010</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molcel.2022.10.010" target="_blank" >10.1016/j.molcel.2022.10.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural and functional basis of mammalian microRNA biogenesis by Dicer

Popis výsledku v původním jazyce

MicroRNA (miRNA) and RNA interference (RNAi) pathways rely on small RNAs produced by Dicer endonucle-ases. Mammalian Dicer primarily supports the essential gene-regulating miRNA pathway, but how it is spe-cifically adapted to miRNA biogenesis is unknown. We show that the adaptation entails a unique structural role of Dicer´s DExD/H helicase domain. Although mice tolerate loss of its putative ATPase function, the com-plete absence of the domain is lethal because it assures high-fidelity miRNA biogenesis. Structures of murine Dicerd???miRNA precursor complexes revealed that the DExD/H domain has a helicase-unrelated structural function. It locks Dicer in a closed state, which facilitates miRNA precursor selection. Transition to a cleav-age-competent open state is stimulated by Dicer-binding protein TARBP2. Absence of the DExD/H domain or its mutations unlocks the closed state, reduces substrate selectivity, and activates RNAi. Thus, the DExD/H domain structurally contributes to mammalian miRNA biogenesis and underlies mechanistical partitioning of miRNA and RNAi pathways.

Název v anglickém jazyce

Structural and functional basis of mammalian microRNA biogenesis by Dicer

Popis výsledku anglicky

MicroRNA (miRNA) and RNA interference (RNAi) pathways rely on small RNAs produced by Dicer endonucle-ases. Mammalian Dicer primarily supports the essential gene-regulating miRNA pathway, but how it is spe-cifically adapted to miRNA biogenesis is unknown. We show that the adaptation entails a unique structural role of Dicer´s DExD/H helicase domain. Although mice tolerate loss of its putative ATPase function, the com-plete absence of the domain is lethal because it assures high-fidelity miRNA biogenesis. Structures of murine Dicerd???miRNA precursor complexes revealed that the DExD/H domain has a helicase-unrelated structural function. It locks Dicer in a closed state, which facilitates miRNA precursor selection. Transition to a cleav-age-competent open state is stimulated by Dicer-binding protein TARBP2. Absence of the DExD/H domain or its mutations unlocks the closed state, reduces substrate selectivity, and activates RNAi. Thus, the DExD/H domain structurally contributes to mammalian miRNA biogenesis and underlies mechanistical partitioning of miRNA and RNAi pathways.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Cell

ISSN

1097-2765

e-ISSN

1097-4164

Svazek periodika

82

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

30

Strana od-do

"4064"-"4079e.13"

Kód UT WoS článku

000898565300011

EID výsledku v databázi Scopus

—