Structural and functional basis of mammalian microRNA
biogenesis by Dicer

J 2022

Structural and functional basis of mammalian microRNA biogenesis by Dicer

ZAPLETAL, David; Eliska TABORSKA; Josef PASULKA; Radek MALIK; Karel KUBÍČEK et. al.

Basic information

Original name

Structural and functional basis of mammalian microRNA biogenesis by Dicer

Authors

Edition

Molecular Cell, CAMBRIDGE, CELL PRESS, 2022, 1097-2765

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 16.000

RIV identification code

RIV/00216224:14740/22:00128561

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1016/j.molcel.2022.10.010

UT WoS

000898565300011

EID Scopus

2-s2.0-85140966014

Keywords in English

CRYO-EM STRUCTUREGUIDE STRAND SELECTIONRNA-BINDINGSTRUCTURE VALIDATIONTRBP COMPLEXMOUSEEXPRESSIONMOLPROBITYSPECIFICITYRECOGNITION

Abstract

In the original language

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.

Links

EF19_073/0016943, research and development project

Name: Interní grantová agentura Masarykovy univerzity

GA22-19896S, research and development project

Name: Strukturní podstata pro opětovné sestavení nukleosomu při přepisu genu zprostředkovaná proteinem Spt6

Investor: Czech Science Foundation, Structural basis for co-transcriptional nucleosome reassembly mediated by Spt6

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

649030, interní kód MU

Name: DECOR - Dynamic assembly and exchange of RNA polymerase II CTD factors (Acronym: DECOR)

Investor: European Union, DECOR, ERC (Excellent Science)

90127, large research infrastructures

Name: CIISB II

90131, large research infrastructures

Name: ELIXIR-CZ II

Cite

ZAPLETAL, David; Eliska TABORSKA; Josef PASULKA; Radek MALIK; Karel KUBÍČEK; Martina ZÁNOVÁ; Christian MUCH; Marek ŠEBESTA; Valeria BUCCHERI; Filip HORVAT; Irena JENICKOVA; Michaela PROCHAZKOVA; Jan PROCHAZKA; Matyáš PINKAS; Jiří NOVÁČEK; Diego F JOSEPH; Radislav SEDLACEK; Carrie BERNECKY; Donal CARROLL; Richard ŠTEFL and Petr SVOBODA. Structural and functional basis of mammalian microRNA biogenesis by Dicer. Molecular Cell. CAMBRIDGE: CELL PRESS, 2022, vol. 82, No 21, p. 4064-4079, 30 pp. ISSN 1097-2765. Available from: https://doi.org/10.1016/j.molcel.2022.10.010.

@article{2252813,
   author = {Zapletal, David and Taborska, Eliska and Pasulka, Josef and Malik, Radek and Kubíček, Karel and Zánová, Martina and Much, Christian and Šebesta, Marek and Buccheri, Valeria and Horvat, Filip and Jenickova, Irena and Prochazkova, Michaela and Prochazka, Jan and Pinkas, Matyáš and Nováček, Jiří and Joseph, Diego F and Sedlacek, Radislav and Bernecky, Carrie and Carroll, Donal and Štefl, Richard and Svoboda, Petr},
   article_location = {CAMBRIDGE},
   article_number = {21},
   doi = {https://doi.org/10.1016/j.molcel.2022.10.010},
   keywords = {CRYO-EM STRUCTUREGUIDE STRAND SELECTIONRNA-BINDINGSTRUCTURE VALIDATIONTRBP COMPLEXMOUSEEXPRESSIONMOLPROBITYSPECIFICITYRECOGNITION},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {Structural and functional basis of mammalian microRNA biogenesis by Dicer},
   url = {https://www.sciencedirect.com/science/article/pii/S1097276522009674?via%3Dihub},
   volume = {82},
   year = {2022}
}

TY  - JOUR
ID  - 2252813
AU  - Zapletal, David - Taborska, Eliska - Pasulka, Josef - Malik, Radek - Kubíček, Karel - Zánová, Martina - Much, Christian - Šebesta, Marek - Buccheri, Valeria - Horvat, Filip - Jenickova, Irena - Prochazkova, Michaela - Prochazka, Jan - Pinkas, Matyáš - Nováček, Jiří - Joseph, Diego F - Sedlacek, Radislav - Bernecky, Carrie - Carroll, Donal - Štefl, Richard - Svoboda, Petr
PY  - 2022
TI  - Structural and functional basis of mammalian microRNA biogenesis by Dicer
JF  - Molecular Cell
VL  - 82
IS  - 21
SP  - 4064-4079
EP  - 4064-4079
PB  - CELL PRESS
SN  - 10972765
KW  - CRYO-EM STRUCTUREGUIDE STRAND SELECTIONRNA-BINDINGSTRUCTURE VALIDATIONTRBP COMPLEXMOUSEEXPRESSIONMOLPROBITYSPECIFICITYRECOGNITION
UR  - https://www.sciencedirect.com/science/article/pii/S1097276522009674?via%3Dihub
N2  - 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.
ER  -

ZAPLETAL, David; Eliska TABORSKA; Josef PASULKA; Radek MALIK; Karel KUBÍČEK; Martina ZÁNOVÁ; Christian MUCH; Marek ŠEBESTA; Valeria BUCCHERI; Filip HORVAT; Irena JENICKOVA; Michaela PROCHAZKOVA; Jan PROCHAZKA; Matyáš PINKAS; Jiří NOVÁČEK; Diego F JOSEPH; Radislav SEDLACEK; Carrie BERNECKY; Donal CARROLL; Richard ŠTEFL and Petr SVOBODA. Structural and functional basis of mammalian microRNA biogenesis by Dicer. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2022, vol.~82, No~21, p.~4064-4079, 30 pp. ISSN~1097-2765. Available from: https://doi.org/10.1016/j.molcel.2022.10.010.

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