SUMMARY PARAGRAPH for KRS1
KRS1 encodes cytoplasmic lysyl-tRNA synthetase (1), the aminoacyl-tRNA synthetase specific for lysine. A second lysyl-tRNA synthetase, Msk1p, is localized to mitochondria. Both the cytoplasmic and mitochondrial enzymes are required for the import of nuclear encoded tRNA(lys)CUU into mitochondria (2).
About aminoacyl-tRNA synthetases...
In a process critical for accurate translation of the genetic code, aminoacyl-tRNA synthetases (aka aminoacyl-tRNA ligases) attach amino acids specifically to cognate tRNAs, thereby "charging" the tRNAs. The catalysis is accomplished via a two-step mechanism. First, the synthetase activates the amino acid in an ATP-dependent reaction, producing aminoacyl-adenylate and releasing inorganic pyrophosphate (PPi). Second, the enzyme binds the correct tRNA and transfers the activated amino acid to either the 2' or 3' terminal hydroxyl group of the tRNA, forming the aminoacyl-tRNA and AMP (3, 4 and references therein).
Aminoacyl-tRNA synthetases possess precise substrate specificity and, despite their similarity in function, vary in size, primary sequence and subunit composition. Individual members of the aminoacyl-tRNA synthetase family can be categorized in one of two classes, depending on amino acid specificity. Class I enzymes (those specific for Glu, Gln, Arg, Cys, Met, Val, Ile, Leu, Tyr and Trp) typically contain two highly conserved sequence motifs, are monomeric or dimeric, and aminoacylate at the 2' terminal hydroxyl of the appropriate tRNA. Class II enzymes (those specific for Gly, Ala, Pro, Ser, Thr, His, Asp, Asn, Lys and Phe) typically contain three highly conserved sequence motifs, are dimeric or tetrameric, and aminoacylate at the 3' terminal hydroxyl of the appropriate tRNA (3, 4, 5 and references therein).
The expression of KRS1 is under general amino acid control and a mutant was initially characterized as a negative regulator of general control of amino acid biosynthesis (6, 1). Further research demonstrated that this Krs1p mutation results in a decrease in lysyl-tRNA concentrations, which initiates a response to amino acid starvation in the cell (7).
Last updated: 2008-07-14