An Ancient Transcription Factor Initiates the Burst of piRNA Production during Early Meiosis in Mouse Testes
Program in Bioinformatics and Integrative Biology; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
RNA, Small Interfering; Transcription Factors; Proto-Oncogene Proteins; Trans-Activators; Avian Proteins
Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during postnatal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feedforward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals.
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Citation: Mol Cell. 2013 Apr 11;50(1):67-81. doi: 10.1016/j.molcel.2013.02.016. Link to article on publisher's site
Li, Xin Zhiguo; Roy, Christian K.; Dong, Xianjun; Bolcun-Filas, Ewelina; Wang, Jie; Han, Bo W.; Xu, Jia; Moore, Melissa J.; Schimenti, John C.; Weng, Zhiping; and Zamore, Phillip D., "An Ancient Transcription Factor Initiates the Burst of piRNA Production during Early Meiosis in Mouse Testes" (2013). Biochemistry and Molecular Pharmacology Publications and Presentations. Paper 157.