dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells

0371756 - ÚMG 2012 RIV GB eng J - Článek v odborném periodiku
Nejepínská, Jana - Malík, Radek - Filkowski, J. - Flemr, Matyáš - Filipowicz, W. - Svoboda, Petr
dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells.
Nucleic Acids Research. Roč. 40, č. 1 (2012), s. 399-413. ISSN 0305-1048. E-ISSN 1362-4962
Grant CEP: GA ČR GA204/09/0085
Grant ostatní: EMBO SDIG(XE) 1483
Výzkumný záměr: CEZ:AV0Z50520514
Klíčová slova: dsRNA * RNAi * interferon
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 8.278, rok: 2012

Double-stranded RNA (dsRNA) can enter sequence-specific RNA interference (RNAi), sequence-independent interferon (IFN) response and editing by adenosine deaminases pathways. To study the fate of dsRNA in vivo, we used transgenic mice ubiquitously expressing from a promoter an mRNA with a long hairpin. The expressed dsRNA did not cause any developmental defects nor activated the IFN response, which was inducible only at high expression levels in cultured cells. dsRNA was poorly processed into siRNAs in somatic cells while robust RNAi effects were found in oocytes, suggesting that somatic cells lack some factor(s) facilitating siRNA biogenesis. Expressed dsRNA did not cause transcriptional silencing in trans. Analysis of RNA editing revealed an edited small fraction of long dsRNA. RNA editing did not prevent cytoplasmic localization nor processing into siRNAs. Thus, a long dsRNA structure is well tolerated in mammalian cells and is mainly causing a robust RNAi response in oocytes.
Trvalý link: http://hdl.handle.net/11104/0205200