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

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 pre-implantation 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 post-transcriptional 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.

SUBMITTER: Dr. Rajika Arora

PROVIDER: S-SCDT-EMBOR-2021-54458V1 | biostudies-other |

REPOSITORIES: biostudies-other

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ADAR1 restricts LINE-1 retrotransposition.

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