Molecular basis of human nuclear and mitochondrial tRNA 3' processing

Area of Science:

• Molecular Biology
• RNA Processing
• Mitochondrial Biology

Background:

• Eukaryotic transfer RNA (tRNA) precursors require precise processing for maturation.
• The enzyme ELAC2 is crucial for 3' end processing of both nuclear-encoded (nu-tRNAs) and mitochondria-encoded (mt-tRNAs) tRNAs in humans.
• ELAC2 functions independently for nu-tRNA processing but necessitates accessory factors for most mt-tRNA processing.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying ELAC2-mediated tRNA 3' end processing, particularly in mitochondria.
• To determine the specific roles of TRMT10C and SDR5C1 in processing structurally degenerate mt-tRNAs.
• To provide a structural basis for organelle-specific tRNA maturation pathways.

Main Methods:

• X-ray crystallography was employed to determine the structures of ELAC2 in complex with TRMT10C, SDR5C1, and mt-tRNA substrates.
• Comparative analysis of protein-RNA and protein-protein interactions involved in tRNA recognition.
• Investigation of the functional significance of TRMT10C-SDR5C1 in compensating for mt-tRNA structural variations.

Main Results:

• TRMT10C and SDR5C1 specifically facilitate the processing of mt-tRNAs that lack a canonical elbow structure.
• Two distinct pre-tRNA recognition mechanisms were identified: direct ELAC2-RNA interaction for canonical tRNAs and ELAC2-TRMT10C protein-protein interaction for noncanonical mt-tRNAs.
• Structural data revealed how TRMT10C and SDR5C1 act as a mitochondrial tRNA maturation platform.

Conclusions:

• The study provides the molecular basis for tRNA 3' processing in both the nucleus and mitochondria.
• The findings explain the organelle-specific requirement for additional factors like TRMT10C and SDR5C1 in mt-tRNA processing.
• TRMT10C-SDR5C1 likely evolved to handle structurally compromised mt-tRNAs prevalent in bilaterian animals.