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Sequestration of LINE-1 in novel cytosolic bodies by MOV10 restricts retrotransposition

Rajika Arora, Maxime Bodak, Laura Penouty, Cindy Hackman, View ORCID ProfileConstance Ciaudo
doi: https://doi.org/10.1101/2021.11.09.467897
Rajika Arora
1Swiss Federal Institute of Technology Zurich, IMHS, Chair of RNAi and Genome Integrity, Zurich, Switzerland
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Maxime Bodak
1Swiss Federal Institute of Technology Zurich, IMHS, Chair of RNAi and Genome Integrity, Zurich, Switzerland
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Laura Penouty
1Swiss Federal Institute of Technology Zurich, IMHS, Chair of RNAi and Genome Integrity, Zurich, Switzerland
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Cindy Hackman
1Swiss Federal Institute of Technology Zurich, IMHS, Chair of RNAi and Genome Integrity, Zurich, Switzerland
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Constance Ciaudo
1Swiss Federal Institute of Technology Zurich, IMHS, Chair of RNAi and Genome Integrity, Zurich, Switzerland
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  • ORCID record for Constance Ciaudo
  • For correspondence: cciaudo@ethz.ch
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Abstract

LINE-1 (L1) are autonomous retroelements that have retained their ability to mobilize. Mechanisms regulating L1 mobility include DNA methylation in somatic cells and the Piwi-interacting RNA pathway in the germline. During pre-implantation stages of mouse embryonic development, however, both pathways are inactivated leading to a critical window necessitating alternate means of L1 regulation. We previously reported an increase in L1 levels in Dicer_KO mouse embryonic stem cells (mESCs). Intriguingly this was accompanied by only a marginal increase in retrotransposition, suggestive of additional mechanisms suppressing L1 mobility. Here, we demonstrate that L1 Ribonucleoprotein complexes (L1 RNP) accumulate as aggregates in Dicer_KO cytoplasm along with the RNA helicase MOV10. The combined overexpression of L1 RNAs and MOV10 is sufficient to create L1 RNP aggregates in stem cells. 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 expression, and its role in preventing L1 retrotransposition by driving novel cytosolic aggregation affords alternate routes to explore for therapy and disease progression.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 09, 2021.
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Sequestration of LINE-1 in novel cytosolic bodies by MOV10 restricts retrotransposition
Rajika Arora, Maxime Bodak, Laura Penouty, Cindy Hackman, Constance Ciaudo
bioRxiv 2021.11.09.467897; doi: https://doi.org/10.1101/2021.11.09.467897
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Sequestration of LINE-1 in novel cytosolic bodies by MOV10 restricts retrotransposition
Rajika Arora, Maxime Bodak, Laura Penouty, Cindy Hackman, Constance Ciaudo
bioRxiv 2021.11.09.467897; doi: https://doi.org/10.1101/2021.11.09.467897

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