Ansgar Zoch, Gabriela Konieczny, Tania Auchynnikava, Birgit Stallmeyer, Nadja Rotte, Madeleine Heep, Rebecca V Berrens, Martina Schito, Yuka Kabayama, Theresa Schöpp, Sabine Kliesch, Brendan Houston, Liina Nagirnaja, Moira K O'Bryan, Kenneth I Aston, Donald F Conrad, Juri Rappsilber, Robin C Allshire, Atlanta G Cook, Frank Tüttelmann, Dónal O'Carroll
In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germ line remain unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of these pathogenic alleles, we discovered that the uncharacterized protein C19ORF84 interacts with SPOCD1...
February 7, 2024: Molecular Cell