Sequestration of LINE-1 in cytosolic aggregates by MOV10 restricts retrotransposition

EMBO Rep. 2022 Sep 5;23(9):e54458. doi: 10.15252/embr.202154458. Epub 2022 Jul 20.

Abstract

LINE-1 (L1) retroelements have retained their ability to mobilize. Mechanisms regulating L1 mobility include DNA methylation in somatic cells and the piRNA pathway in the germline. During preimplantation stages of mouse embryonic development, however, both pathways are inactivated leading to a window necessitating alternate means of L1 regulation. We previously reported an increase in L1 levels in Dicer_KO mouse embryonic stem cells (mESCs), which was accompanied by only a marginal increase in retrotransposition, suggesting additional mechanisms suppressing L1 mobility. Here, we demonstrate that L1 ribonucleoprotein complexes (L1 RNP) accumulate as aggregates in the cytoplasm of Dicer_KO mESCs along with the RNA helicase MOV10. The combined overexpression of L1 ORF1p and MOV10 is sufficient to create L1 RNP aggregates. In Dicer_KO mESCs, MOV10 is upregulated due to the loss of its direct regulation by miRNAs. The newly discovered posttranscriptional regulation of Mov10, and its role in preventing L1 retrotransposition by driving cytosolic aggregation, provides routes to explore for therapy in disease conditions where L1s are upregulated.

Keywords: LINE-1; MOV10; cytosolic aggregates; miRNA; retrotransposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryonic Development*
  • Long Interspersed Nucleotide Elements
  • Mice
  • MicroRNAs* / metabolism
  • RNA, Small Interfering / metabolism
  • Retroelements / genetics

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • Retroelements