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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

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

2024

Kód důvěrnosti údajů

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

Název periodika

Embo Reports

ISSN

1469-221X

e-ISSN

1469-3178

Svazek periodika

25

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

2896-2913

Kód UT WoS článku

001228186600001

EID výsledku v databázi Scopus

2-s2.0-85193540577