9HLZ

Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome

This is a non-PDB format compatible entry.

Summary for 9HLZ

• Entry DOI: 10.2210/pdb9hlz/pdb
• EMDB information: 52281
• Descriptor: Small ribosomal subunit protein mS38, Small ribosomal subunit protein uS2m, Small ribosomal subunit protein uS3m, ... (81 entities in total)
• Functional Keywords: mitoribosome, translation, ribosome
• Biological source: Saccharomyces cerevisiae W303; More
• Total number of polymer chains: 79
• Total formula weight: 3769713.66

Authors

Carlstrom, A.,Rovsnik, U.,Ott, M. (deposition date: 2024-12-06, release date: 2025-12-17)

Primary citation

Bridgers, J.B.,Carlstrom, A.,Sherpa, D.,Couvillion, M.T.,Rovsnik, U.,Gao, J.,Wan, B.,Shao, S.,Ott, M.,Churchman, L.S.
Translational activators align mRNAs at the small mitoribosomal subunit for translation initiation.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Mitochondrial gene expression is essential for oxidative phosphorylation. Mitochondrial-encoded mRNAs are translated by dedicated mitochondrial ribosomes (mitoribosomes), whose regulation remains elusive. In Saccharomyces cerevisiae, nuclear-encoded mitochondrial translational activators (TAs) facilitate transcript-specific translation by a yet unknown mechanism. Here, we investigated the function of TAs containing RNA-binding pentatricopeptide repeats using selective mitoribosome profiling and cryo-electron microscopy (cryo-EM) structural analysis. These analyses show that TAs exhibit strong selectivity for mitoribosomes initiating on their target transcripts. Moreover, TA-mitoribosome footprints indicate that TAs recruit mitoribosomes proximal to the start codon. Two cryo-EM structures of mRNA-TA complexes bound to mitoribosomes stalled in the post-initiation, pre-elongation state revealed the general mechanism of TA action. Specifically, the TAs bind to structural elements in the 5' untranslated region of the client mRNA and the mRNA channel exit to align the mRNA in the small subunit during initiation. Our findings provide a mechanistic basis for understanding how mitochondria achieve transcript-specific translation initiation without relying on general sequence elements to position mitoribosomes at start codons.

PubMed: 41339860
DOI: 10.1038/s41594-025-01726-y

Experimental method

ELECTRON MICROSCOPY (3.2 Å)