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PMID: 20547853 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 26 ·2010-06-29 ·Pages 11847-52

Frost RJ, Hamra FK, Richardson JA, Qi X, Bassel-Duby R, Olson EN

Abstract

Piwi-interacting RNAs (piRNAs) comprise a broad class of small noncoding RNAs that function as an endogenous defense system against transposable elements. Here we show that the putative DExD-box helicase MOV10-like-1 (MOV10L1) is essential for silencing retrotransposons in the mouse male germline. Mov10l1 is specifically expressed in germ cells with increasing expression from gonocytes/type A spermatogonia to pachytene spermatocytes. Primary spermatocytes of Mov10l1(-/-) mice show activation of LTR and LINE-1 retrotransposons, followed by cell death, causing male infertility and a complete block of spermatogenesis at early prophase of meiosis I. Despite the early expression of Mov10l1, germline stem cell maintenance appears unaffected in Mov10l1(-/-) mice. MOV10L1 interacts with the Piwi proteins MILI and MIWI. MOV10L1 also interacts with heat shock 70-kDa protein 2 (HSPA2), a testis-enriched chaperone expressed in pachytene spermatocytes and also essential for male fertility. These studies reveal a crucial role of MOV10L1 in male fertility and piRNA-directed retrotransposon silencing in male germ cells and suggest that MOV10L1 functions as a key component of a safeguard mechanism for the genetic information in male germ cells of mammals.

MeSH Terms
Amino Acid Sequence Animals Argonaute Proteins Base Sequence DNA Methylation DNA Primers/genetics Fertility HSP70 Heat-Shock Proteins/metabolism Male Meiosis Mice Mice, Knockout Models, Biological Molecular Sequence Data Mutation Proteins/metabolism RNA Helicases/deficiency,genetics,metabolism RNA, Small Interfering/genetics,metabolism Retroelements/genetics Sequence Homology, Amino Acid Spermatocytes/metabolism Spermatogenesis Testis/metabolism
Chemicals
Argonaute Proteins DNA Primers HSP70 Heat-Shock Proteins Hspa2 protein, mouse Piwil1 protein, mouse Piwil2 protein, mouse Proteins RNA, Small Interfering Retroelements Mov10l1 protein, mouse RNA Helicases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Frost Robert J A
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Hamra F Kent
Richardson James A
Qi Xiaoxia
Bassel-Duby Rhonda
Olson Eric N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1007158107
Published
2010-06-29
Epub
2010-00-14
Pages
11847-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2900665
Subset
IM
Grants
NICHD NIH HHS · R01 HD036022-10 · United States
NICHD NIH HHS · R01 HD036022 · United States
NICHD NIH HHS · R01 HD053889 · United States
NHLBI NIH HHS · R01 HL093039 · United States
NICHD NIH HHS · R01 HD036022-09 · United States
NICHD NIH HHS · R01 HD061575 · United States
External Links
PubMed source DOI: 10.1073/pnas.1007158107 PMC Full Text View journal details
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