NONU-1 encodes a conserved endonuclease required for mRNA translation surveillance

• DOI: 10.1101/674358
• Publication Date: 2019-06-19T03:26:12Z
• Authors: Marissa L. Glover; A. Max. Burroughs; Thea A. Egelhofer; Makena N. Pule; L. Aravind; Joshua A. Arribere
• Keywords: 0301 basic medicine; 03 medical and health sciences

ABSTRACTCellular translation surveillance rescues ribosomes that stall on problematic mRNAs. During translation surveillance, endonucleolytic cleavage of the problematic mRNA is a critical step in rescuing stalled ribosomes. However, the nuclease(s) responsible remain unknown. Here we identify NONU-1 as a novel endoribonuclease required for translation surveillance pathways including No-Go and Nonstop mRNA Decay. We show that: (1) NONU-1 reduces Nonstop and No-Go mRNA levels; (2) NONU-1 contains an Smr RNase domain required for mRNA decay and with properties similar to the unknown endonuclease; and (3) the domain architecture and catalytic residues of NONU-1 are conserved throughout metazoans and eukaryotes, respectively. We extend our results inC. elegansto homologous factors inS. cerevisiae, showing conservation of function of the NONU-1 protein across billions of years of evolution. Our work establishes the identity of a previously unknown factor critical to translation surveillance and will inform mechanistic studies at the intersection of translation and mRNA decay.