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>