Functional defects of pathogenic human mitochondrial tRNAs related to structural fragility

摘要: Aminoacylation of transfer RNAs (tRNAs) is essential for protein synthesis. A growing number human diseases correlate with point mutations in tRNA genes within the mitochondrial genome. These tRNAs have unique sequences that suggest they fragile structures. However, structural significance pathology-related and their effects on molecular function not been explored. Here, opthalmoplegia related mutants a investigated. Each mutation replaces either an A-U or G-C pair predicted secondary structure A-C pair. each mutant was severely attenuated. Moreover, strongly inhibited aminoacylation wild type substrate, suggesting these might be bypassed potentially heteroplasmic environment mitochondria. The rescued by single compensatory restored Watson-Crick base pairing reintroduced stability into regions structure, even though pairs introduced were different from those found tRNA. Thus, functional defects caused subset pathogenic may result inherent fragility tRNAs.