The Transcription Factor A-Myb Initiates Pachytene piRNA Production During Mouse Spermatogenesis

In animals, germ cells require PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. In mammals, transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later in sperm development and account for >95% of all piRNAs in adult mouse testes. Without pachytene piRNAs, mice fail to produce functional sperm , but neither the molecular function nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-Myb initiates pachytene piRNAs production. A-Myb drives transcription of both pachytene piRNA precursor RNAs and the mRNA encoding Miwi, the Argonaute protein through which pachytene piRNAs function. Together, A-Myb and Miwi create a conserved feed-forward loop that ensures the rapid accumulation of pachytene piRNAs.