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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
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 |
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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 |
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