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About 2000 completely sequenced mitochondrial genomes are available from the NCBI RefSeq data base together with manually curated annotations of their protein-coding genes, rRNAs, and tRNAs. This annotation information, which has accumulated over two decades, has been obtained with a diverse set of computational tools and annotation strategies. Despite all(More)
Correct expression of the genetic code at translation is directly correlated with tRNA identity. This survey describes the molecular signals in tRNAs that trigger specific aminoacylations. For most tRNAs, determinants are located at the two distal extremities: the anticodon loop and the amino acid accepting stem. In a few tRNAs, however, major identity(More)
Transfer RNAs (tRNAs) are present in all types of cells as well as in organelles. tRNAs of animal mitochondria show a low level of primary sequence conservation and exhibit 'bizarre' secondary structures, lacking complete domains of the common cloverleaf. Such sequences are hard to detect and hence frequently missed in computational analyses and(More)
Post-transcriptional modifications are characteristic features of tRNAs and have been shown in a number of cases to influence both their structural and functional properties, including structure stabilization, amino-acylation and codon recognition. We have developed an approach which allows the investigation of the post-transcriptional modification patterns(More)
A growing number of mutated mitochondrial tRNA genes have been found associated with severe human diseases. To investigate the potential interference of such mutations with the primordial function of tRNAs, i.e. their aminoacylation by cognate aminoacyl-tRNA synthetases, a human mitochondrial in vitro aminoacylation system specific for isoleucine has been(More)
The molecular recognition of specific transfer RNAs by the appropriate aminoacyl-tRNA synthetase is an important step in determining the accuracy of translation of the genetic message from nucleic acids into proteins. Recent studies using variant tRNAs with specific sequence modifications have indicated particular regions that determine their identity. Here(More)
Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.Val213Phe]) is the underlying cause of nonsyndromic hearing loss (DFNB94) and compound heterozygous mutations ([c.969T>A; p.Tyr323*] + [c.1142A>G; p.Asn381Ser]) result in(More)
The mitochondrial genome of metazoan animal typically encodes 22 tRNAs. Nematode mt-tRNAs normally lack the T-stem and instead feature a replacement loop. In the class Enoplea, putative mt-tRNAs that are even further reduced have been predicted to lack both the T- and the D-arm. Here we investigate these tRNA candidates in detail. Three lines of(More)
The human mitochondrial genome encodes 22 tRNAs interspersed among the two rRNAs and 11 mRNAs, often without spacers, suggesting that tRNAs must be efficiently excised. Numerous maternally transmitted diseases and syndromes arise from mutations in mitochondrial tRNAs, likely due to defect(s) in tRNA metabolism. We have systematically explored the effect of(More)
A number of point mutations in human mitochondrial (mt) tRNA genes are correlated with a variety of neuromuscular and other severe disorders including encephalopathies, myopathies, cardiopathies and diabetes. The complexity of the genotype/phenotype relationships, the diversity of possible molecular impacts of the different mutations at the tRNA(More)