title: Human mitochondrial tRNA quality control in health and disease: a channelling mechanism?
abstract: Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. These single nucleotide substitutions in various domains of tRNA molecules may affect different steps of tRNA biogenesis. Often, the prominent decrease of aminoacylation and/or steady-state levels of affected mitochondrial tRNA have been demonstrated in patients' tissues and in cultured cells. Similar effect has been observed for pathogenic mutations in nuclear genes encoding mitochondrial aminoacyl-tRNA-synthetases, while over-expression of mitochondrial aminoacyl-tRNA synthetases or elongation factor EF-Tu rescued mutated tRNAs from degradation. In this review we summarize experimental data concerning the possible regulatory mechanisms governing mitochondrial tRNA steady-state levels, and propose a hypothesis based on the tRNA channelling principle. According to this hypothesis, interaction of mitochondrial tRNA with proteins ensures not only tRNA synthesis, maturation and function, but also protection from degradation. Mutations perturbing this interaction lead to decreased tRNA stability.
authors.affiliation: Division of Pediatric Nephrology, Shaare Zedek Medical Center; Jerusalem, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Belostotsky
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Frishberg
authors.forename: Nina
authors.initials: N
authors.lastname: Entelis
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics / Q000378:metabolism; D049148:Aminoacylation; D050259:Genes, Mitochondrial; D015894:Genome, Human; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010444:Peptide Elongation Factor Tu / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; C091648:TUFM protein, human; D012313:RNA; D012343:RNA, Transfer; D010444:Peptide Elongation Factor Tu; D000604:Amino Acyl-tRNA Synthetases