RT Journal Article SR Electronic T1 PETISCO is a novel protein complex required for 21U RNA biogenesis and embryonic viability JF bioRxiv FD Cold Spring Harbor Laboratory SP 463711 DO 10.1101/463711 A1 Ricardo J. Cordeiro Rodrigues A1 António Miguel de Jesus Domingues A1 Svenja Hellmann A1 Sabrina Dietz A1 Bruno F. M. de Albuquerque A1 Christian Renz A1 Helle D. Ulrich A1 Falk Butter A1 René F. Ketting YR 2018 UL http://biorxiv.org/content/early/2018/11/07/463711.abstract AB Piwi proteins are important for germ cell development in almost all animals studied thus far. These proteins are guided to specific targets, such as transposable elements, by small guide RNAs, often referred to as piRNAs, or 21U RNAs in C. elegans. In this organism, even though genetic screens have uncovered a number of potential 21U RNA biogenesis factors, little is known about how these factors interact or what they do. Based on the previously identified 21U biogenesis factor PID-1, we here define a novel protein complex, PETISCO, that is required for 21U RNA biogenesis. PETISCO contains both potential 5’-cap and 5’-phosphate RNA binding domains, suggesting involvement in 5’ end processing. We define the interaction architecture of PETISCO and reveal a second function for PETISCO in embryonic development. This essential function of PETISCO is not mediated by PID-1, but by TOST-1. Vice versa, TOST-1 is not involved in 21U RNA biogenesis. Both PID-1 and TOST-1 are small, intrinsically disordered proteins that interact directly with the PETISCO protein ERH-2 (enhancer of rudimentary homolog 2) using a conserved sequence motif. Finally, our data suggest an important role for TOST-1:PETISCO in SL1 homeostasis in the early embryo. Our work describes the first molecular platform for 21U RNA production in C. elegans, and strengthens the view that 21U RNA biogenesis is built upon a much more widely used, snRNA-related pathway.