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Publication : MFN2 interacts with nuage-associated proteins and is essential for male germ cell development by controlling mRNA fate during spermatogenesis.

First Author  Wang X Year  2021
Journal  Development Volume  148
Issue  7 PubMed ID  33674260
Mgi Jnum  J:305430 Mgi Id  MGI:6710299
Doi  10.1242/dev.196295 Citation  Wang X, et al. (2021) MFN2 interacts with nuage-associated proteins and is essential for male germ cell development by controlling mRNA fate during spermatogenesis. Development 148(7):dev196295
abstractText  Mitochondria play a crucial role in spermatogenesis and are regulated by several mitochondrial fusion proteins. However, their functional importance associated with their structure formation and mRNA fate regulation during spermatogenesis remains unclear. Here, we show that mitofusin 2 (MFN2), a mitochondrial fusion protein, interacts with nuage-associated proteins (including MIWI, DDX4, TDRKH and GASZ) in mice. Conditional mutation of Mfn2 in postnatal germ cells results in male sterility due to germ cell developmental defects. Moreover, MFN2 interacts with MFN1, another mitochondrial fusion protein with a high-sequence similarity to MFN2, in testes to facilitate spermatogenesis. Simultaneous mutation of Mfn1 and Mfn2 in testes causes very severe infertile phenotypes. Importantly, we show that MFN2 is enriched in polysome fractions of testes and interacts with MSY2, a germ cell-specific DNA/RNA-binding protein, to control gamete-specific mRNA (such as Spata19) translational activity during spermatogenesis. Collectively, our findings demonstrate that MFN2 interacts with nuage-associated proteins and MSY2 to regulate male germ cell development by controlling several gamete-specific mRNA fates.
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