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Structural basis of TACO1-mediated efficient mitochondrial translation.

Shuhui Wang1, Michele Brischigliaro2, Yuekang Zhang1

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

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The mitochondrial translation accelerator TACO1 aids protein synthesis by binding human mitoribosomes, preventing stalling during challenging sequences like polyproline motifs.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • Protein synthesis relies on translation elongation factors interacting with the ribosomal L7/L12 stalk.
  • Mitochondrial translation requires specific factors for efficient elongation.

Purpose of the Study:

  • To elucidate the mechanism of the mitochondrial translation accelerator TACO1 in human mitoribosomes.
  • To understand TACO1's role in preventing translation stalling.

Main Methods:

  • In organello cryo-electron microscopy (cryo-EM) of human mitoribosomes.
  • Structural analysis of TACO1-mitoribosome interactions.
  • Investigating the impact of TACO1 absence on translation dynamics.

Main Results:

  • TACO1 binds human mitoribosomes, bridging subunits and interacting with rRNA and ribosomal proteins.
  • TACO1 stabilizes A-site tRNA and enhances peptidyl transfer, distinct from other factors.
  • TACO1 is crucial for efficient translation of polyproline motifs, preventing ribosome stalling and subunit dissociation.

Conclusions:

  • TACO1 is a key factor for efficient mitochondrial translation elongation, particularly for challenging sequences.
  • TACO1 employs a unique mechanism to promote elongation, competing with elongation factor Tu.
  • These findings suggest conserved roles for TACO1 orthologs in maintaining translation efficiency across species.