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Mili Interacts with Tudor Domain-Containing Protein 1 in Regulating Spermatogenesis

2009; Elsevier BV; Volume: 19; Issue: 8 Linguagem: Inglês

10.1016/j.cub.2009.02.061

1879-0445

Jianquan Wang, Jonathan P. Saxe, Takashi Tanaka, Shinichiro Chuma, Haifan Lin,

Advanced biosensing and bioanalysis techniques

Piwi proteins are essential for germline development, stem cell self-renewal, epigenetic regulation, and transposon silencing [1Cox D.N. Chao A. Baker J. Chang L. Qiao D. Lin H. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal.Genes Dev. 1998; 12: 3715-3727Crossref PubMed Scopus (761) Google Scholar, 2Cox D.N. Chao A. Lin H. piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells.Development. 2000; 127: 503-514PubMed Google Scholar, 3Lin H. Spradling A.C. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary.Development. 1997; 124: 2463-2476Crossref PubMed Google Scholar, 4Pal-Bhadra M. Leibovitch B.A. Gandhi S.G. Rao M. Bhadra U. Birchler J.A. Elgin S.C. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery.Science. 2004; 303: 669-672Crossref PubMed Scopus (549) Google Scholar, 5Brower-Toland B. Findley S.D. Jiang L. Liu L. Yin H. Dus M. Zhou P. Elgin S.C. Lin H. Drosophila PIWI associates with chromatin and interacts directly with HP1a.Genes Dev. 2007; 21: 2300-2311Crossref PubMed Scopus (257) Google Scholar, 6Yin H. Lin H. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster.Nature. 2007; 450: 304-308Crossref PubMed Scopus (316) Google Scholar, 7Aravin A.A. Sachidanandam R. Girard A. Fejes-Toth K. Hannon G.J. Developmentally regulated piRNA clusters implicate MILI in transposon control.Science. 2007; 316: 744-747Crossref PubMed Scopus (690) Google Scholar]. They bind to a complex class of small noncoding RNAs called Piwi-interacting RNAs (piRNAs) [8Lin H. piRNAs in the germ line.Science. 2007; 316: 397Crossref PubMed Scopus (115) Google Scholar]. Mammalian Piwi proteins such as Mili are localized in the cytoplasm of spermatogenic cells, where they are associated with a germline-specific organelle called the nuage or its derivative, the chromatoid body, as well as with polysomes [9Unhavaithaya Y. Hao Y. Beyret E. Yin H. Kuramochi-Miyagawa S. Nakano T. Lin H. MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation.J. Biol. Chem. 2009; 284: 6507-6519Crossref PubMed Scopus (157) Google Scholar]. To investigate the molecular mechanisms mediated by Mili, we searched for Mili-interacting proteins. Here, we report that Mili specifically interacts with Tudor domain-containing protein 1 (Tdrd1), a germline protein that contains multiple Tudor domains [10Chuma S. Hiyoshi M. Yamamoto A. Hosokawa M. Takamune K. Nakatsuji N. Mouse Tudor Repeat-1 (MTR-1) is a novel component of chromatoid bodies/nuages in male germ cells and forms a complex with snRNPs.Mech. Dev. 2003; 120: 979-990Crossref PubMed Scopus (97) Google Scholar, 11Chuma S. Hosokawa M. Kitamura K. Kasai S. Fujioka M. Hiyoshi M. Takamune K. Noce T. Nakatsuji N. Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice.Proc. Natl. Acad. Sci. USA. 2006; 103: 15894-15899Crossref PubMed Scopus (177) Google Scholar]. This RNA-independent interaction is mediated through the N-terminal domain of Mili and the N-terminal region of Tdrd1 containing the myeloid Nervy DEAF-1 (MYND) domain and the first two Tudor domains. In addition, Mili positively regulates the expression of the Tdrd1 mRNA. Furthermore, Mili and Tdrd1 mutants share similar spermatogenic defects. However, Tdrd1, unlike Mili, is not required for piRNA biogenesis. Our results suggest that Mili interacts with Tdrd1 in the nuage and chromatoid body. This interaction does not contribute to piRNA biogenesis but represents a regulatory mechanism that is critical for spermatogenesis.