Functional Proteomics Identifies a PICS Complex Required for piRNA Maturation and Chromosome Segregation

Abstract

Summary: piRNAs play significant roles in suppressing transposons and nonself nucleic acids, maintaining genome integrity, and defending against viral infections. In C. elegans, piRNA precursors are transcribed in the nucleus and are subjected to a number of processing and maturation steps. The biogenesis of piRNAs is not fully understood. We use functional proteomics in C. elegans and identify a piRNA biogenesis and chromosome segregation (PICS) complex. The PICS complex contains TOFU-6, PID-1, PICS-1, TOST-1, and ERH-2, which exhibit dynamic localization among different subcellular compartments. In the germlines, the PICS complex contains TOFU-6/PICS-1/ERH-2/PID-1, is largely concentrated at the perinuclear granule zone, and engages in piRNA processing. During embryogenesis, the TOFU-6/PICS-1/ERH-2/TOST-1 complex accumulates in the nucleus and plays essential roles in chromosome segregation. The functions of these factors in mediating chromosome segregation are independent of piRNA production. We speculate that differential compositions of PICS factors may help cells coordinate distinct cellular processes. : Zeng et al. use functional proteomics and identify a PICS complex that promotes Piwi-interacting RNA (piRNA) production in C. elegans. This work reports that the PICS complex acts in the 5′ end processing of piRNA precursors. This PICS complex also shuttles between the nucleus and cytoplasm and promotes chromosome segregation in embryos. Keywords: piRNA, TOFU-6, PID-1, TOST-1, PICS-1, ERH-2, chromosome segregation, perinuclear granule