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Cytoplasmic Compartmentalization of the Fetal piRNA Pathway in Mice

Aravin, Alexei A. and van der Heijden, Godfried W. and Castañeda, Julio and Vagin, Vasily V. and Hannon, Gregory J. and Bortvin, Alex (2009) Cytoplasmic Compartmentalization of the Fetal piRNA Pathway in Mice. PLOS Genetics, 5 (12). Art. No. e1000764. ISSN 1553-7404. PMCID PMC2785470. https://resolver.caltech.edu/CaltechAUTHORS:20190508-111702371

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Abstract

Derepression of transposable elements (TEs) in the course of epigenetic reprogramming of the mouse embryonic germline necessitates the existence of a robust defense that is comprised of PIWI/piRNA pathway and de novo DNA methylation machinery. To gain further insight into biogenesis and function of piRNAs, we studied the intracellular localization of piRNA pathway components and used the combination of genetic, molecular, and cell biological approaches to examine the performance of the piRNA pathway in germ cells of mice lacking Maelstrom (MAEL), an evolutionarily conserved protein implicated in transposon silencing in fruit flies and mice. Here we show that principal components of the fetal piRNA pathway, MILI and MIWI2 proteins, localize to two distinct types of germinal cytoplasmic granules and exhibit differential association with components of the mRNA degradation/translational repression machinery. The first type of granules, pi-bodies, contains the MILI-TDRD1 module of the piRNA pathway and is likely equivalent to the enigmatic “cementing material” first described in electron micrographs of rat gonocytes over 35 years ago. The second type of granules, piP-bodies, harbors the MIWI2-TDRD9-MAEL module of the piRNA pathway and signature components of P-bodies, GW182, DCP1a, DDX6/p54, and XRN1 proteins. piP-bodies are found predominantly in the proximity of pi-bodies and the two frequently share mouse VASA homolog (MVH) protein, an RNA helicase. In Mael-mutant gonocytes, MIWI2, TDRD9, and MVH are lost from piP-bodies, whereas no effects on pi-body composition are observed. Further analysis revealed that MAEL appears to specifically facilitate MIWI2-dependent aspects of the piRNA pathway including biogenesis of secondary piRNAs, de novo DNA methylation, and efficient downregulation of TEs. Cumulatively, our data reveal elaborate cytoplasmic compartmentalization of the fetal piRNA pathway that relies on MAEL function.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1371/journal.pgen.1000764DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785470PubMed CentralArticle
https://doi.org/10.1371/journal.pgen.1000764.s001DOIFigure S1
https://doi.org/10.1371/journal.pgen.1000764.s002DOIFigure S2
https://doi.org/10.1371/journal.pgen.1000764.s003DOIFigure S3
https://doi.org/10.1371/journal.pgen.1000764.s004DOIFigure S4
https://doi.org/10.1371/journal.pgen.1000764.s005DOIFigure S5
https://doi.org/10.1371/journal.pgen.1000764.s006DOIFigure S6
https://doi.org/10.1371/journal.pgen.1000764.s007DOIFigure S7
https://doi.org/10.1371/journal.pgen.1000764.s008DOIFigure S8
https://doi.org/10.1371/journal.pgen.1000764.s009DOITable S1
Additional Information:© 2009 Aravin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received July 28, 2009; Accepted November 11, 2009; Published December 11, 2009. GJH is an investigator of the Howard Hughes Medical Institute. This work was supported by Carnegie Institution of Washington, grants from the National Institutes of Health to GJH, and by an NIH Pathway to Independence Award K99HD057233 to AAA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist. We thank S.L. Martin, D. Pezic, S. Chuma, E.K. Chan, and S. Tajima for sharing their antibodies. We thank Eugenia Dikovsky and the animal facility staff for their invaluable help and Michael Sepanski for assistance and expertise with EM studies (Carnegie Institution). We thank Maria Mosquera, Lisa Bianco, Jodi Coblentz, and Gula Nourjanova (CSHL) for animal assistance and histology and Michelle Rooks, Dick Mccombie, Danea Rabbolini, and Laura Cardone for help with Illumina sequencing (CSHL). Author Contributions: Conceived and designed the experiments: AAA GWvdH GJH AB. Performed the experiments: AAA GWvdH AB. Analyzed the data: AAA GWvdH GJH AB. Contributed reagents/materials/analysis tools: JC VVV. Wrote the paper: AAA GWvdH GJH AB.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Carnegie Institution of WashingtonUNSPECIFIED
NIHK99HD057233
Issue or Number:12
PubMed Central ID:PMC2785470
Record Number:CaltechAUTHORS:20190508-111702371
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190508-111702371
Official Citation:Aravin AA, van der Heijden GW, Castan˜eda J, Vagin VV, Hannon GJ, et al. (2009) Cytoplasmic Compartmentalization of the Fetal piRNA Pathway in Mice. PLoS Genet 5(12): e1000764. doi:10.1371/journal.pgen.1000764
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95348
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 May 2019 17:51
Last Modified:03 Oct 2019 21:12

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