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Sequestration of LINE ‐1 in cytosolic aggregates by MOV10 restricts retrotransposition
Author(s) -
Arora Rajika,
Bodak Maxime,
Penouty Laura,
Hackman Cindy,
Ciaudo Constance
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202154458
Subject(s) - dicer , microbiology and biotechnology , downregulation and upregulation , biology , somatic cell , ribonucleoprotein , retrotransposon , embryonic stem cell , rna interference , rna , chemistry , genetics , gene , transposable element , genome
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.