10.1371/journal.pgen.1003791 Constance Ciaudo Constance Ciaudo Florence Jay Florence Jay Ikuhiro Okamoto Ikuhiro Okamoto Chong-Jian Chen Chong-Jian Chen Alexis Sarazin Alexis Sarazin Nicolas Servant Nicolas Servant Emmanuel Barillot Emmanuel Barillot Edith Heard Edith Heard Olivier Voinnet Olivier Voinnet RNAi-Dependent and Independent Control of LINE1 Accumulation and Mobility in Mouse Embryonic Stem Cells Public Library of Science 2013 line1 accumulation mobility embryonic 2013-11-07 02:58:54 Dataset https://plos.figshare.com/articles/dataset/_RNAi_Dependent_and_Independent_Control_of_LINE1_Accumulation_and_Mobility_in_Mouse_Embryonic_Stem_Cells_/843813 <div><p>In most mouse tissues, long-interspersed elements-1 (L1s) are silenced <i>via</i> 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 <i>Dicer<sup>−/−</sup></i> 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 <i>Dicer<sup>−/−</sup></i> mESCs.</p></div>