MIWI arginines orchestrate generation of functional pachytene piRNAs and spermiogenesis

Mouse MIWI (PIWIL1) binds to pachytene piRNAs, the most abundant, sequence-diverse and rapidly evolving class of small RNAs. Here we report that N-terminal arginines (NTR) of MIWI, by coordinating interactions with Tudor domain containing proteins (TDRDs) required for piRNA biogenesis, orchestrate the functions of MIWI and piRNAs. MIWI-NTRs mediate piRNA amplification, which is necessary for both transposon control and for sustaining levels of select, nonconserved, pachytene piRNAs that target specific mRNAs required for spermiogenesis. Our findings support the notion that the vast majority of pachytene piRNAs are dispensable, acting as autonomous genetic elements that rely for propagation on MIWI piRNA amplification, the ancestral mechanism for piRNA mediated transposon control. MIWI-NTRs also mediate interactions with TDRD6 that are necessary for Chromatoid Body compaction. Furthermore, MIWI-NTRs promote stabilization of spermiogenic transcripts that drive nuclear compaction, which is essential for sperm formation, indicating distinct roles for MIWI and TDRD6 in spermiogenesis.