Cargando…

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

Double-stranded RNA (dsRNA) can enter different pathways in mammalian cells, including sequence-specific RNA interference (RNAi), sequence-independent interferon (IFN) response and editing by adenosine deaminases. To study the routing of dsRNA to these pathways in vivo, we used transgenic mice ubiqu...

Descripción completa

Detalles Bibliográficos
Autores principales: Nejepinska, Jana, Malik, Radek, Filkowski, Jody, Flemr, Matyas, Filipowicz, Witold, Svoboda, Petr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245926/
https://www.ncbi.nlm.nih.gov/pubmed/21908396
http://dx.doi.org/10.1093/nar/gkr702
_version_ 1782219908084400128
author Nejepinska, Jana
Malik, Radek
Filkowski, Jody
Flemr, Matyas
Filipowicz, Witold
Svoboda, Petr
author_facet Nejepinska, Jana
Malik, Radek
Filkowski, Jody
Flemr, Matyas
Filipowicz, Witold
Svoboda, Petr
author_sort Nejepinska, Jana
collection PubMed
description Double-stranded RNA (dsRNA) can enter different pathways in mammalian cells, including sequence-specific RNA interference (RNAi), sequence-independent interferon (IFN) response and editing by adenosine deaminases. To study the routing of dsRNA to these pathways in vivo, we used transgenic mice ubiquitously expressing from a strong promoter, an mRNA with a long hairpin in its 3′-UTR. The expressed dsRNA neither caused any developmental defects nor activated the IFN response, which was inducible only at high expression levels in cultured cells. The dsRNA was poorly processed into siRNAs in somatic cells, whereas, 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 that a small fraction of long dsRNA is edited. RNA editing neither prevented the 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.
format Online
Article
Text
id pubmed-3245926
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-32459262012-01-03 dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells Nejepinska, Jana Malik, Radek Filkowski, Jody Flemr, Matyas Filipowicz, Witold Svoboda, Petr Nucleic Acids Res RNA Double-stranded RNA (dsRNA) can enter different pathways in mammalian cells, including sequence-specific RNA interference (RNAi), sequence-independent interferon (IFN) response and editing by adenosine deaminases. To study the routing of dsRNA to these pathways in vivo, we used transgenic mice ubiquitously expressing from a strong promoter, an mRNA with a long hairpin in its 3′-UTR. The expressed dsRNA neither caused any developmental defects nor activated the IFN response, which was inducible only at high expression levels in cultured cells. The dsRNA was poorly processed into siRNAs in somatic cells, whereas, 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 that a small fraction of long dsRNA is edited. RNA editing neither prevented the 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. Oxford University Press 2012-01 2011-09-08 /pmc/articles/PMC3245926/ /pubmed/21908396 http://dx.doi.org/10.1093/nar/gkr702 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Nejepinska, Jana
Malik, Radek
Filkowski, Jody
Flemr, Matyas
Filipowicz, Witold
Svoboda, Petr
dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells
title dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells
title_full dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells
title_fullStr dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells
title_full_unstemmed dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells
title_short dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells
title_sort dsrna expression in the mouse elicits rnai in oocytes and low adenosine deamination in somatic cells
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245926/
https://www.ncbi.nlm.nih.gov/pubmed/21908396
http://dx.doi.org/10.1093/nar/gkr702
work_keys_str_mv AT nejepinskajana dsrnaexpressioninthemouseelicitsrnaiinoocytesandlowadenosinedeaminationinsomaticcells
AT malikradek dsrnaexpressioninthemouseelicitsrnaiinoocytesandlowadenosinedeaminationinsomaticcells
AT filkowskijody dsrnaexpressioninthemouseelicitsrnaiinoocytesandlowadenosinedeaminationinsomaticcells
AT flemrmatyas dsrnaexpressioninthemouseelicitsrnaiinoocytesandlowadenosinedeaminationinsomaticcells
AT filipowiczwitold dsrnaexpressioninthemouseelicitsrnaiinoocytesandlowadenosinedeaminationinsomaticcells
AT svobodapetr dsrnaexpressioninthemouseelicitsrnaiinoocytesandlowadenosinedeaminationinsomaticcells