Structural basis of mitochondrial translation

• DOI: 10.7554/elife.58362
• Publication Date: 2020-08-19T14:00:49Z
• Authors: Shintaro Aibara; Vivek Singh; Angelika Modelska; Alexey Amunts
• Keywords: Models, Molecular; Ribosomal Proteins; 0301 basic medicine; QH301-705.5; RNA, Mitochondrial; Science; Structural Biology and Molecular Biophysics; translation; Mitochondrial Proteins; Mitochondrial Ribosomes; 03 medical and health sciences; RNA, Transfer; Humans; RNA, Messenger; Biology (General); Q; R; RNA-Binding Proteins; Mitochondria; Neoplasm Proteins; mitochondria; HEK293 Cells; ribosome; Protein Biosynthesis; gene expression; RNA; cryo-EM; Medicine

Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 Å resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.