Functional canonical RNAi in mice expressing a truncated Dicer isoform and long dsRNA

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00601090" target="_blank" >RIV/68378050:_____/24:00601090 - isvavai.cz</a>
Result on the web
<a href="https://www.embopress.org/doi/full/10.1038/s44319-024-00148-z" target="_blank" >https://www.embopress.org/doi/full/10.1038/s44319-024-00148-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s44319-024-00148-z" target="_blank" >10.1038/s44319-024-00148-z</a>

Result language
angličtina
Original language name
Functional canonical RNAi in mice expressing a truncated Dicer isoform and long dsRNA
Original language description
Canonical RNA interference (RNAi) is sequence-specific mRNA degradation guided by small interfering RNAs (siRNAs) made by RNase III Dicer from long double-stranded RNA (dsRNA). RNAi roles include gene regulation, antiviral immunity or defense against transposable elements. In mammals, RNAi is constrained by Dicer's adaptation to produce another small RNA class-microRNAs. However, a truncated Dicer isoform (Delta HEL1) supporting RNAi exists in mouse oocytes. A homozygous mutation to express only the truncated Delta HEL1 variant causes dysregulation of microRNAs and perinatal lethality in mice. Here, we report the phenotype and canonical RNAi activity in Dicer Delta HEL1/wt mice, which are viable, show minimal miRNome changes, but their endogenous siRNA levels are an order of magnitude higher. We show that siRNA production in vivo is limited by available dsRNA, but not by Protein kinase R, a dsRNA sensor of innate immunity. dsRNA expression from a transgene yields sufficient siRNA levels to induce efficient RNAi in heart and muscle. Dicer Delta HEL1/wt mice with enhanced canonical RNAi offer a platform for examining potential and limits of mammalian RNAi in vivo.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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