Structural basis of TACO1-mediated efficient mitochondrial translation.

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.