Figure 7. miRNAs‐mediated control of MOV10 expression regulates L1 retrotransposition in mESCs.

The life cycle of L1 retrotransposition is depicted as a model. Only full‐length L1 elements get transcribed driven by the promoter residing in its 5'UTR sequence. The bicistronic L1 RNA is exported from the nucleus into the cytosol and translated to give rise to L1 ORF1 (ORF1p) and L1 ORF2 (ORF2p) proteins. The L1 RNA and proteins form a complex (L1 RNP) and are imported back into the nucleus. Endonuclease activity of ORF2 nicks the target DNA and using a mechanism referred to as target primed reverse transcription a new copy of L1 element is inserted into the genome via a copy past mechanism of mobilization (Beck et al, ²⁰¹¹; Goodier, ²⁰¹⁶). A key regulatory step for retrotransposition is the import of L1RNP back into the nucleus. The canonical miRNA biogenesis pathway illustrates the miRNAs discovered in this study that regulate expression of RNA helicase Mov10 a known modulator of L1 mobility. In the absence of miRNAs when either DICER or DROSHA proteins are deleted in mESCs, both L1 and MOV10 expression are upregulated. Our data suggest that in miRNA, mutant mESCs MOV10 induces L1 RNP aggregate formation in the cytoplasm, the impaired import consequently prevents L1 retrotransposition despite high L1 expression. While DDX6 was also found to co‐localize with the larger L1 RNP particles, the identification of molecular partners and biochemical activities intrinsic to the L1 RNP aggregates should unveil the bottle neck afforded to prevent import.