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Structural and functional basis of mammalian microRNA biogenesis by Dicer
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SYSNO ASEP 0567393 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Structural and functional basis of mammalian microRNA biogenesis by Dicer Author(s) Zapletal, D. (CZ)
Táborská, Eliška (UMG-J)
Pasulka, Josef (UMG-J)
Malík, Radek (UMG-J) RID
Kubíček, Karel (UMG-J)
Zanova, M. (CZ)
Much, C. (IT)
Šebesta, M. (CZ)
Buccheri, Valeria (UMG-J)
Horvat, Filip (UMG-J)
Jeníčková, Irena (UMG-J)
Procházková, Michaela (UMG-J)
Procházka, Jan (UMG-J) ORCID
Pinkas, M. (CZ)
Nováček, J. (CZ)
Florian Joseph, Diego André (UMG-J)
Sedláček, Radislav (UMG-J) RID
Bernecky, C. (AT)
O'Carroll, D. (GB)
Štefl, R. (CZ)
Svoboda, Petr (UMG-J) RIDNumber of authors 21 Source Title Molecular Cell. - : Cell Press - ISSN 1097-2765
Roč. 82, č. 21 (2022), s. 4064-4079e.13Number of pages 30 s. Language eng - English Country US - United States Keywords cryo-em structure ; guide strand selection ; rna-binding ; structure validation ; expression ; molprobity ; trbp complex ; mouse ; specifity OECD category Biochemistry and molecular biology R&D Projects LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018131 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GX20-03950X GA ČR - Czech Science Foundation (CSF) EF18_046/0015861 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure e-INFRA CZ - 90140 - CESNET, zájmové sdružení právnických osob
CIISB II - 90127 - Masarykova univerzitaMethod of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000898565300011 DOI 10.1016/j.molcel.2022.10.010 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2023 Electronic address https://doi.org/10.1016/j.molcel.2022.10.010
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