anticodon and Genetic-Diseases--Inborn

Transfer RNAs (tRNAs) harbor the most diverse posttranscriptional modifications. Among such modifications, those in the anticodon loop, either on nucleosides or base groups, compose over half of the identified posttranscriptional modifications. The derivatives of modified nucleotides and the crosstalk of different chemical modifications further add to the structural and functional complexity of tRNAs. These modifications play critical roles in maintaining anticodon loop conformation, wobble base pairing, efficient aminoacylation, and translation speed and fidelity as well as mediating various responses to different stress conditions. Posttranscriptional modifications of tRNA are catalyzed mainly by enzymes and/or cofactors encoded by nuclear genes, whose mutations are firmly connected with diverse human diseases involving genetic nervous system disorders and/or the onset of multisystem failure. In this review, we summarize recent studies about the mechanisms of tRNA modifications occurring at tRNA anticodon loops. In addition, the pathogenesis of related disease-causing mutations at these genes is briefly described.

Topics: Anticodon; Base Pairing; Escherichia coli; Genetic Diseases, Inborn; Humans; Nucleic Acid Conformation; RNA Processing, Post-Transcriptional; RNA, Transfer; Saccharomyces cerevisiae

Topics: Anticodon; Codon; Genetic Diseases, Inborn; Humans; Protein Biosynthesis; RNA, Transfer

Several point mutations in mitochondrial tRNA genes have been linked to distinct clinical subgroups of mitochondrial diseases. A particularly large number of different mutations is found in the tRNA(Leu)(UUR) gene. We show that base substitutions at nucleotide position 3256, 3260, and 3271 of the mitochondrial genome, located in the D and anticodon stem of this tRNA, and mutation 3243 changing a base involved in a tertiary interaction, significantly impair the processing of the tRNA precursor in vitro. In correlation with other studies, our results suggest that inefficient processing of certain mutant variants of mitochondrial tRNA(Leu)(UUR) is a primary molecular impairment leading to mitochondrial dysfunction and consequently to disease.

Topics: Anticodon; Base Sequence; Codon; Endoribonucleases; Genetic Diseases, Inborn; Genetic Variation; Humans; Mitochondrial Myopathies; Molecular Sequence Data; Nucleic Acid Conformation; Point Mutation; Ribonuclease P; RNA; RNA, Catalytic; RNA, Mitochondrial; RNA, Transfer, Leu