C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline

In the male mouse germline, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide the DNA methylation of young active transposable elements (TEs) through SPOCD1. We identified loss-of-function variants in human SPOCD1 that cause male infertility and defective TE silencing. One SPOCD1 pathogenic allele encodes a truncated protein that lacks the conserved carboxy-terminus. We demonstrated that this deleted region interacts with C19ORF84. In mouse foetal germ cells, the nuclear protein C19ORF84 is required for the association of SPOCD1 with DNMT3L, an essential component of the de novo methylation machinery. In summary, we identified a conserved role for SPOCD1 in safeguarding the continuity of the human germline and discovered C19ORF84, an uncharacterised protein essential for 15 orchestrating piRNA-directed DNA methylation.

Dónal O'Carroll, Ansgar Zoch & Rebecca Berrens (2024). C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline. BioStudies, E-MTAB-11612. Retrieved from https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-11612