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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-11-01
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| Series: | PLoS Genetics |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244175/pdf/?tool=EBI |
| _version_ | 1818701867168825344 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T15:27:39Z |
| format | Article |
| id | doaj.art-63eb929027224e2ca85621dfb61baf93 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-17T15:27:39Z |
| publishDate | 2013-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-63eb929027224e2ca85621dfb61baf932022-12-21T21:43:14ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-11-01911e100379110.1371/journal.pgen.1003791RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.Constance CiaudoFlorence JayIkuhiro OkamotoChong-Jian ChenAlexis SarazinNicolas ServantEmmanuel BarillotEdith HeardOlivier VoinnetIn 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244175/pdf/?tool=EBI |
| spellingShingle | 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. PLoS Genetics |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244175/pdf/?tool=EBI |
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