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,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. © 2013 ciaudo et al.