Structural basis of mitochondrial translation

Elife. 2020 Aug 19;9:e58362. doi: 10.7554/eLife.58362.

Abstract

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.

Keywords: RNA; cryo-EM; gene expression; human; mitochondria; molecular biophysics; ribosome; structural biology; translation.

MeSH terms

  • HEK293 Cells
  • Humans
  • Mitochondria / physiology
  • Mitochondria / ultrastructure*
  • Mitochondrial Proteins / biosynthesis*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Ribosomes / physiology
  • Mitochondrial Ribosomes / ultrastructure*
  • Models, Molecular
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism
  • RNA, Mitochondrial / metabolism
  • RNA, Transfer / metabolism
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • Ribosomal Proteins / biosynthesis*
  • Ribosomal Proteins / genetics

Substances

  • LRPPRC protein, human
  • Mitochondrial Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Mitochondrial
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • SLIRP protein, human
  • mitochondrial messenger RNA
  • RNA, Transfer