Ubiquitination of stalled ribosomes enables mRNA decay via HBS-1 and NONU-1 in vivo

• DOI: 10.1371/journal.pgen.1010577
• Publication Date: 2023-01-10T19:05:02Z
• Authors: Parissa C. Monem; Nitin Vidyasagar; Audrey L. Piatt; Enisha Sehgal; Joshua A. Arribere
• Keywords: 0301 basic medicine; 0303 health sciences; Saccharomyces cerevisiae Proteins; RNA Stability; Ubiquitination; Saccharomyces cerevisiae; QH426-470; 03 medical and health sciences; Protein Biosynthesis; Genetics; Animals; RNA, Messenger; Caenorhabditis elegans; Ribosomes; Research Article

As ribosomes translate the genetic code, they can encounter a variety of obstacles that hinder their progress. If stall for prolonged times, cells suffer due to loss translating and accumulation aberrant protein products. Thus protect cells, stalled experience series reactions relieve degrade offending mRNA, process known as No-Go mRNA Decay (NGD). While much machinery NGD is known, precise ordering events factors along this pathway has not been tested. Here, we deploy C . elegans unravel coordinated comprising NGD. Utilizing novel reporter forward reverse genetics, identify required Our subsequent molecular analyses define functional requirement ubiquitination on at least two ribosomal proteins (eS10 uS10), show lacking sites eS10 uS10 fail perform in vivo We nuclease NONU-1 acts after ubiquitin ligase ZNF-598, discover ribosome rescue HBS-1/PELO-1 decay via NONU-1. Taken together, our work demonstrates mechanisms by which signal effectors repression, delineate links between repressive working toward well-defined pathway.