Meioc-Piwil1 complexes regulate rRNA transcription for differentiation of spermatogonial stem cells.

Ribosome biogenesis is vital for sustaining stem cell properties, yet its regulatory mechanisms are obscure. Herein, we show unique properties of zebrafish meioc mutants in which spermatogonial stem cells (SSCs) do not differentiate or upregulate rRNAs. Meioc colocalized with Piwil1 in perinuclear germ granules, but Meioc depletion resulted in Piwil1 accumulation in nucleoli. Nucleolar Piwil1 interacted with 45S pre-rRNA. piwil1 ^+/- spermatogonia with reduced Piwil1 upregulated rRNAs, and piwil1 ^+/- ;meioc ^-/- spermatogonia recovered differentiation later than those in meioc ^-/- . Further, Piwil1 interacted with Setdb1 and HP1α, and meioc ^-/- spermatogonia exhibited high levels of H3K9me3 and methylated CpG in the 45S-rDNA region. These results indicate that zebrafish SSCs silence rRNA transcription with repressive marks similar to Drosophila piRNA targets of RNA polymerase II, and that Meioc has a unique function on preventing localization of Piwil1 in nucleoli to upregulate rRNA transcripts and to promote SSC differentiation.
Competing Interests: Competing interest statement: The authors declare no competing financial interests.