Structural basis of 3′-tRNA maturation by the human mitochondrial RNase Z complex
Genís Valentín Gesé, B.M. Hallberg
Abstract
Abstract Maturation of human mitochondrial tRNA is essential for cellular energy production, yet the underlying mechanisms remain only partially understood. Here, we present several cryo-EM structures of the mitochondrial RNase Z complex (ELAC2/SDR5C1/TRMT10C) bound to different maturation states of mitochondrial tRNA His , showing the molecular basis for tRNA-substrate selection and catalysis. Our structural insights provide a molecular rationale for the 5′-to-3′ tRNA processing order in mitochondria, the 3′-CCA antideterminant effect, and the basis for sequence-independent recognition of mitochondrial tRNA substrates. Furthermore, our study links mutations in ELAC2 to clinically relevant mitochondrial diseases, offering a deeper understanding of the molecular defects contributing to these conditions.