Elongational stalling activates mitoribosome-associated quality control

• Published in: Science (American Association for the Advancement of Science) Vol. 370; no. 6520; pp. 1105 - 1110
• Main Authors: Desai, Nirupa, Yang, Hanting, Chandrasekaran, Viswanathan, Kazi, Razina, Minczuk, Michal, Ramakrishnan, V
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 27.11.2020
• Subjects: Adenosine triphosphate; ATP; Chains; Cryoelectron Microscopy; Electron microscopy; Electron Transport Complex IV - chemistry; Elongated structure; Escherichia coli; Exoribonucleases - genetics; Genomes; HEK293 Cells; Homology; Humans; Intermediates; Metabolites; Microscopy; Mitochondria; Mitochondrial Proteins - chemistry; Mitochondrial Ribosomes - chemistry; Nuclear Proteins - chemistry; Oxidation; Oxidative phosphorylation; Peptide Termination Factors - chemistry; Phosphorylation; Polypeptides; Protein Domains; Proteins; Quality control; Ribonucleic acid; Ribosomal Proteins - chemistry; Ribosomes; RNA; RNA, Transfer - chemistry; RNA-binding protein; RNA-Binding Proteins - chemistry; Stalling; Synthesis; Transcription Elongation, Genetic; Transcriptional Elongation Factors - chemistry; Transfer RNA; Translation; Translation elongation; Translocase; Triphosphatase; tRNA
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abc7782

The human mitochondrial ribosome (mitoribosome) and associated proteins regulate the synthesis of 13 essential subunits of the oxidative phosphorylation complexes. We report the discovery of a mitoribosome-associated quality control pathway that responds to interruptions during elongation, and we present structures at 3.1- to 3.3-angstrom resolution of mitoribosomal large subunits trapped during ribosome rescue. Release factor homolog C12orf65 (mtRF-R) and RNA binding protein C6orf203 (MTRES1) eject the nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for these factors during mitoribosome rescue. We also report related cryo-electron microscopy structures (3.7 to 4.4 angstrom resolution) of elongating mitoribosomes bound to tRNAs, nascent polypeptides, the guanosine triphosphatase elongation factors mtEF-Tu and mtEF-G1, and the Oxa1L translocase.