RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.

In most mouse tissues, long-interspersed elements-1 (L1s) are silenced via methylation of their 5'-untranslated regions (5'-UTR). A gradual loss-of-methylation in pre-implantation embryos coincides with L1 retrotransposition in blastocysts, generating potentially harmful mutations. Here, w...

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Autores principales:	Constance Ciaudo, Florence Jay, Ikuhiro Okamoto, Chong-Jian Chen, Alexis Sarazin, Nicolas Servant, Emmanuel Barillot, Edith Heard, Olivier Voinnet
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/63eb929027224e2ca85621dfb61baf93
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spelling	oai:doaj.org-article:63eb929027224e2ca85621dfb61baf932021-11-18T06:21:36ZRNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.1553-73901553-740410.1371/journal.pgen.1003791https://doaj.org/article/63eb929027224e2ca85621dfb61baf932013-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244175/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404In most mouse tissues, long-interspersed elements-1 (L1s) are silenced via methylation of their 5'-untranslated regions (5'-UTR). A gradual loss-of-methylation in pre-implantation embryos coincides with L1 retrotransposition in blastocysts, generating potentially harmful mutations. Here, we show that Dicer- and Ago2-dependent RNAi restricts L1 accumulation and retrotransposition in undifferentiated mouse embryonic stem cells (mESCs), derived from blastocysts. RNAi correlates with production of Dicer-dependent 22-nt small RNAs mapping to overlapping sense/antisense transcripts produced from the L1 5'-UTR. However, RNA-surveillance pathways simultaneously degrade these transcripts and, consequently, confound the anti-L1 RNAi response. In Dicer(-/-) mESC complementation experiments involving ectopic Dicer expression, L1 silencing was rescued in cells in which microRNAs remained strongly depleted. Furthermore, these cells proliferated and differentiated normally, unlike their non-complemented counterparts. These results shed new light on L1 biology, uncover defensive, in addition to regulatory roles for RNAi, and raise questions on the differentiation defects of Dicer(-/-) mESCs.Constance CiaudoFlorence JayIkuhiro OkamotoChong-Jian ChenAlexis SarazinNicolas ServantEmmanuel BarillotEdith HeardOlivier VoinnetPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 11, p e1003791 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Constance Ciaudo Florence Jay Ikuhiro Okamoto Chong-Jian Chen Alexis Sarazin Nicolas Servant Emmanuel Barillot Edith Heard Olivier Voinnet RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.
description	In most mouse tissues, long-interspersed elements-1 (L1s) are silenced via methylation of their 5'-untranslated regions (5'-UTR). A gradual loss-of-methylation in pre-implantation embryos coincides with L1 retrotransposition in blastocysts, generating potentially harmful mutations. Here, we show that Dicer- and Ago2-dependent RNAi restricts L1 accumulation and retrotransposition in undifferentiated mouse embryonic stem cells (mESCs), derived from blastocysts. RNAi correlates with production of Dicer-dependent 22-nt small RNAs mapping to overlapping sense/antisense transcripts produced from the L1 5'-UTR. However, RNA-surveillance pathways simultaneously degrade these transcripts and, consequently, confound the anti-L1 RNAi response. In Dicer(-/-) mESC complementation experiments involving ectopic Dicer expression, L1 silencing was rescued in cells in which microRNAs remained strongly depleted. Furthermore, these cells proliferated and differentiated normally, unlike their non-complemented counterparts. These results shed new light on L1 biology, uncover defensive, in addition to regulatory roles for RNAi, and raise questions on the differentiation defects of Dicer(-/-) mESCs.
format	article
author	Constance Ciaudo Florence Jay Ikuhiro Okamoto Chong-Jian Chen Alexis Sarazin Nicolas Servant Emmanuel Barillot Edith Heard Olivier Voinnet
author_facet	Constance Ciaudo Florence Jay Ikuhiro Okamoto Chong-Jian Chen Alexis Sarazin Nicolas Servant Emmanuel Barillot Edith Heard Olivier Voinnet
author_sort	Constance Ciaudo
title	RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.
title_short	RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.
title_full	RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.
title_fullStr	RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.
title_full_unstemmed	RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.
title_sort	rnai-dependent and independent control of line1 accumulation and mobility in mouse embryonic stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/63eb929027224e2ca85621dfb61baf93
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RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.

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