Structural basis of mitochondrial translation

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.

Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi

“…This structural rearrangement during mtSSU rotation suggests a coordinated movement of the mtSSU rotation and mL108 to the L1 stalk. The involvement of mitochondria-specific elements in coordination of tRNA movement has been recently reported also in other systems 20–22 .…”

Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi

“…coordinated movement of the mtSSU rotation and mL108 to the L1 stalk. The involvement of mitochondria-specific elements in coordination of tRNA movement has been recently reported also in other systems [21][22][23] .…”

Interconnected assembly factors regulate the biogenesis of mitoribosomal large subunit

“…In mitochondria, the mtLSU lacks many of the rRNA components involved in the canonical pathways, and higher complexity of the interactions between the mitoribosomal proteins at the functional sites has evolved (Ott et al, 2016;Greber & Ban, 2016). A functional mtLSU requires a folded rRNA core, a flexible L1 stalk that is involved in tRNA movement, an extended L7/L12 protrusion for binding of translational factors, and a proteinaceous CP formed by mitochondria-specific elements involved in tRNA binding (Aibara et al, 2020;Tobiasson & Amunts, 2020). However, only the final stage of the mtLSU assembly with fully mature functional sites has been visualized (Brown et al, 2017;Itoh et al, 2020), and no preceding steps in the formation have been detected.…”