+Search query
-Structure paper
| Title | Translational activators align mRNAs at the small mitoribosomal subunit for translation initiation. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Year 2025 |
| Publish date | Dec 3, 2025 |
Authors | Joseph B Bridgers / Andreas Carlström / Dawafuti Sherpa / Mary T Couvillion / Urška Rovšnik / Jingjing Gao / Bowen Wan / Sichen Shao / Martin Ott / L Stirling Churchman / ![]() |
| PubMed Abstract | Mitochondrial gene expression is essential for oxidative phosphorylation. Mitochondrial-encoded mRNAs are translated by dedicated mitochondrial ribosomes (mitoribosomes), whose regulation remains ...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. |
External links | Nat Struct Mol Biol / PubMed:41339860 |
| Methods | EM (single particle) |
| Resolution | 2.82 - 4.4 Å |
| Structure data | ![]() EMDB-48387: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome ![]() EMDB-48388: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (Small ribosomal subunit) ![]() EMDB-48390: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (large ribosomal subunit) ![]() EMDB-48700: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (composite map SSU and Aep1-Aep2-Atp25 complex) ![]() EMDB-52235: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (consensus) ![]() EMDB-52252: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (focused on the SSU body) ![]() EMDB-52256: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (focused on the SSU head) ![]() EMDB-52257: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (focused on the LSU) ![]() EMDB-52270: Translational activators Aep1, Aep2 and Atp25 in complex with mRNA and the yeast mitochondrial ribosome (focused on Aep1-Aep2-Atp25) ![]() EMDB-52276: Translational activator Aep3 in complex with mRNA and the yeast mitochondrial ribosome (focused on Aep3) ![]() EMDB-52277: Translational activator Aep3 in complex with mRNA and the yeast mitochondrial ribosome (consensus map) ![]() EMDB-52278: Translational activator Aep3 in complex with mRNA and the yeast mitochondrial ribosome (focused on the SSU) ![]() EMDB-52279: Translational activator Aep3 in complex with mRNA and the yeast mitochondrial ribosome (focused on the SSU head) ![]() EMDB-52280: Translational activator Aep3 in complex with mRNA and the yeast mitochondrial ribosome (focused on the LSU) EMDB-52281, PDB-9hlz: EMDB-52283, PDB-9hm0: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-GTP: |
| Source |
|
Keywords | RIBOSOME / Mitoribosome / translation |
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors

External links




















Keywords