Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice

Abstract

Significance Large parts of eukaryotic genomes are composed of transposons. Mammalian genomes use DNA methylation to silence these genomic parasites. A class of small RNAs called Piwi-interacting RNAs (piRNAs) is used to specifically guide the DNA methylation machinery to the transposon DNA elements. How germ cells make piRNAs is not entirely understood. We identify a mouse protein and demonstrate its importance for transposon silencing. We find that the protein collaborates with other factors already implicated in piRNA production. Moreover, the protein is required for piRNA production and assembly of the nuclear silencing complex. Physiological importance of the protein is highlighted by the fact that male mice lacking the protein are infertile. This study will greatly benefit the field of germ-cell biology.

Mutation in TDRD9 causes non-obstructive azoospermia in infertile men

“…TDRD5 (also called meiosis arrest female 1, MARF1) is essential for oogenesis and the development of healthy offspring 32. TDRD proteins were demonstrated to be essential for male mice fertility including Tdrd1,33 Tdrd12,34 Tdrkh35 and Tdrd5 36. Only recently was a TDRD1 polymorphic variant in the 5’-UTR of exon 1 reported to associate with spermatogenic failure susceptibility in a dominant model in the Han Chines 37.…”

Germ granule-mediated RNA regulation in male germ cells

“…The ping-pong amplification mechanism is particularly predominant in fetal male germ cells that are challenged by the global resetting of the male germline epigenome, which causes an induction of the transposon expression. To initiate the amplification cycle in mice, MILI associates with primary piRNAs and operates in the ping-pong cycle together with other factors to yield antisense secondary piRNAs that in turn associate with MIWI2 (De Fazio et al 2011, Pandey et al 2013, Yang et al 2015. MIWI2 then translocates to the nucleus where it initiates transcriptional transposon silencing via DNA methylation at the target loci (Aravin et al 2008, Kuramochi-Miyagawa et al 2008, De Fazio et al 2011.…”

Association of a TDRD1 variant with spermatogenic failure susceptibility in the Han Chinese

“…However, the exact functional mechanism of Piwi/ piRNA complexes remains unclear. Based on the findings of all reviewed studies, piRNA biogenesis-associated genes have been shown to be vital for spermatogenesis [32].…”