Distinct pre-initiation steps in human mitochondrial translation

Khawaja, A.; Itoh, Y.; Remes, C.; Spahr, H.; Yukhnovets, O.; Hofig, H.; Amunts, A.; Rorbach, J.

doi:10.1038/s41467-020-16503-2

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Distinct pre-initiation steps in human mitochondrial translation

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Rorbach, J.
Rorbach – Mitochondrial Gene Expression, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/32522994
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Citation

Khawaja, A., Itoh, Y., Remes, C., Spahr, H., Yukhnovets, O., Hofig, H., et al. (2020). Distinct pre-initiation steps in human mitochondrial translation. Nat Commun, 11(1), 2932. doi:10.1038/s41467-020-16503-2.

Cite as: https://hdl.handle.net/21.11116/0000-000B-30BD-A

Abstract

Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammalian protein synthesis that are specific to mitochondria.