Disease relevance of VARS

• Here, we constructed G3A and G7A mutations into the F proteins of SV5 (W3A and WR isolates), Newcastle disease virus (NDV), and human parainfluenza virus type 3 (HPIV3) [1].
• A purification method for valyl-tRNA synthetase from Bacillus stearothermophilus is described that uses two affinity columns, one containing the pure cognate tRNA, and the other containing all tRNA species except the cognate tRNA [2].

High impact information on VARS

• As well, there was strong support for the monophyly (sensu Hennig) of Archaea. The valyl-tRNA synthetase gene from Tr. vaginalis clustered with other eukaryotic ValRS genes, which may have been transferred from the mitochondrial genome to the nuclear genome, suggesting that this amitochondrial trichomonad once harbored an endosymbiotic bacterium [3].
• The results demonstrate that the NH2-terminal extension of valyl-tRNA synthetase is required for complex formation and that the enzyme-binding site(s) resides on the EF-1 delta subunit [4].
• Reconstitution in vitro of the valyl-tRNA synthetase-elongation factor (EF) 1 beta gamma delta complex. Essential roles of the NH2-terminal extension of valyl-tRNA synthetase and of the EF-1 delta subunit in complex formation [4].
• Our results are essentially in agreement with those from a recent report (Motorin, Y., Wolfson, A., Orlovsky, A., and Gladilin, K. (1988) FEBS Lett. 238, 262-264), according to which the polypeptides other than that assigned to valyl-tRNA synthetase correspond to the subunits of Elongation Factor 1H [5].
• In addition to valyl-tRNA synthetase activity, which was assigned to the 140-kDa component, the purified complex exhibits a potent Elongation Factor 1 activity, determined by its ability to sustain poly(U)-dependent polyphenylalanine synthesis in the presence of Elongation Factor 2 [5].

Biological context of VARS

• Evidence that gene G7a in the human major histocompatibility complex encodes valyl-tRNA synthetase [6].
• To further investigate the connection of mistranslation to cell pathology, we introduced an inducible transgene expressing an editing-deficient valyl-tRNA synthetase into mammalian cells [7].
• Valyl-tRNA synthetase form yellow lupin seeds: hydrolysis of the enzyme-bound noncognate aminoacyl adenylate as a possible mechanism of increasing specificity of the aminoacyl-tRNA synthetase [8].
• For isoleucyl- (IleRS) and valyl-tRNA synthetases (ValRS), reactions that hydrolyze misactivated noncognate amino acids help to achieve high accuracy in aminoacylation [9].
• Floral homeotic gene expression defines developmental arrest stages in Brassica oleracea L. vars. botrytis and italica [10].

Anatomical context of VARS

• The isolation of the valyl-tRNA synthetase mutant reported here brings to eight the number of different aminoacyl-tRNA synthetase mutants isolated in the CHO cell line [11].

Associations of VARS with chemical compounds

• To examine the role of the NH2-terminal extension of mammalian valyl-tRNA synthetase in complex formation and to identify the subunit(s) of EF-1H responsible for binding the enzyme, reconstitution experiments were undertaken [4].
• The mechanism of inhibition of valyl-tRNA synthetase by S-adenosylhomocysteine [12].
• Multiple phosphorylation sites and quaternary organization of guanine-nucleotide exchange complex of elongation factor-1 (EF-1betagammadelta/ValRS) control the various functions of EF-1alpha [13].
• Pyrophosphorolysis and enzymatic hydrolysis of [14C]Val-tRNA catalysed by lupin valyl-tRNA synthetase are inhibited by sodium chloride nearly to the same extent [14].
• S-Adenosylhomocysteine is a competitive inhibitor of the lupin valyl-tRNA synthetase with respect to ATP and valine in the ATP-PPi exchange reaction, noncompetitive with respect to ATP and valine and uncompetitive with respect to tRNA in the tRNA aminoacylation reaction [12].

Physical interactions of VARS

• As a continuation of our studies on plant (yellow lupin, Lupinus luteus) aminoacyl-tRNA synthetases we describe here formation and some properties of valyl-tRNA synthetase-bound valyl adenylate (EVal(Val-AMP)) and seryl-tRNA synthetase-bound seryl adenylate (ESer(Ser-AMP)) [15].

Other interactions of VARS

• These results suggest that A. aeolicus LeuRS carries editing properties that seem more primitive than those of IleRS and ValRS [16].
• In seven of these eight mutants, the in vitro specific activity of a single aminoacyl-tRNA synthetase was greatly reduced; four had reduced levels of histidyl-tRNA synthetase, two of valyl-tRNA synthetase, and one of leucyl-tRNA synthetase [11].

Analytical, diagnostic and therapeutic context of VARS

• Valyl-tRNA synthetase consists of one polypeptide chain of molecular weight 125000 as judged by Sephadex G-200 gel filtration and dodecylsulfate-polyacrylamide gel electrophoresis in the presence of reducing agent [17].
• Genomic structure and sequence analysis of the valyl-tRNA synthetase gene of the Japanese pufferfish, Fugu rubripes [18].

References