Structural and mechanistic basis of RNA processing by protein-only ribonuclease P enzymes

One of the first specialized collections of nucleic acid sequences in life sciences was the ‘compilation of tRNA sequences and sequences of tRNA genes’ (http://www.trna.uni-bayreuth.de). Here, an updated and completely restructured version of this compilation is presented (http://trnadb.bioinf.uni-leipzig.de). The new database, tRNAdb, is hosted and maintained in cooperation between the universities of Leipzig, Marburg, and Strasbourg. Reimplemented as a relational database, tRNAdb will be updated periodically and is searchable in a highly flexible and user-friendly way. Currently, it contains more than 12 000 tRNA genes, classified into families according to amino acid specificity. Furthermore, the implementation of the NCBI taxonomy tree facilitates phylogeny-related queries. The database provides various services including graphical representations of tRNA secondary structures, a customizable output of aligned or un-aligned sequences with a variety of individual and combinable search criteria, as well as the construction of consensus sequences for any selected set of tRNAs.

Mitochondria are eukaryotic organelles that generate most of the energy in the cell by oxidative phosphorylation (OXPHOS). Each mitochondrion contains multiple copies of a closed circular double-stranded DNA genome (mtDNA). Human (mammalian) mtDNA encodes 13 essential subunits of the inner membrane complex responsible for OXPHOS. These mRNAs are translated by the mitochondrial protein synthesis machinery, which uses the 22 species of mitochondrial tRNAs (mt tRNAs) encoded by mtDNA. The unique structural features of mt tRNAs distinguish them from cytoplasmic tRNAs bearing the canonical cloverleaf structure. The genes encoding mt tRNAs are highly susceptible to point mutations, which are a primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. A large number of nuclear factors involved in the biogenesis and function of mt tRNAs have been identified and characterized, including processing endonucleases, tRNA-modifying enzymes, and aminoacyl-tRNA synthetases. These nuclear factors are also targets of pathogenic mutations linked to various diseases, indicating the functional importance of mt tRNAs for mitochondrial activity.