Disease relevance of Transfer RNA Aminoacylation

• Molecular mimicry in translational control of E. coli threonyl-tRNA synthetase gene. Competitive inhibition in tRNA aminoacylation and operator-repressor recognition switch using tRNA identity rules [1].
• Immunoblotting and cDNA cloning studies reveal that the autoantigens of the multisystem autoimmune diseases are important proteins involved in nucleic acid metabolism, including tRNA charging, intron splicing, DNA uncoiling, and RNA polymerase co-factors [2].

High impact information on Transfer RNA Aminoacylation

• Kinetic analysis of heterodimers formed between variant enzymes with defective tyrosine activation or tRNA aminoacylation shows that a molecule of tRNATyr interacts with the N-terminal region of one subunit and the C-terminal region of the other subunit in the dimer [3].
• These findings indicate that ProRS and LeuRS associate in M. thermautotrophicus and suggest that this interaction contributes to translational fidelity by enhancing tRNA aminoacylation by ProRS [4].
• They behave as alpha2 dimers and display catalytic parameters in the tRNA aminoacylation reaction identical to those determined for the native, complex-associated form of aspartyl-tRNA synthetase isolated from rat liver [5].
• However, three acceptor stem derivatives (tRNA(Trp)/C1.G72, tRNA(Trp)/C2.G71, and tRNA(Trp)/A3.U70) required overexpression for growth at 42 degrees C. Northern analysis of these derivatives following acid/urea gel electrophoresis showed no defects in tRNA aminoacylation at the nonpermissive temperature [6].
• The purified glutamyl-tRNA synthetase was identified as the chloroplast enzyme by its tRNA charging specificity [7].

Biological context of Transfer RNA Aminoacylation

• The GluRS apoenzyme fails to show significant kinetics of tRNA aminoacylation and charges unfractionated yeast tRNA at a level 10-fold reduced compared to Arc1p-bound GluRS [8].
• Using in vitro tRNA transcripts and minihelices it was shown that the tyrosine identity for tRNA charging by tyrosyl-tRNA synthetase (TyrRS) from the archaeon Methanococcus jannaschii is determined by six nucleotides: the discriminator base A73 and the first base-pair C1-G72 in the acceptor stem together with the anticodon triplet [9].
• The topography of the active site of histidyl-tRNA synthetase has been investigated by determining Ki values for a variety of structural analogues of histidine, using the ATP-PPi exchange and tRNA aminoacylation reactions [10].

Anatomical context of Transfer RNA Aminoacylation

• Ribosome bypassing at serine codons as a test of the model of selective transfer RNA charging [11].
• Furthermore, our results indicate that cyclosporin A (inhibitor of lymphocyte activation) blocks the Concanavalin A stimulation of tRNA charging ranging from 16 to 93% [12].
• Isolation and characterization of an estrogen-regulated ribosome-associated inactivator of tRNA aminoacylation in the uterus [13].

Associations of Transfer RNA Aminoacylation with chemical compounds

• The effect is more pronounced on the tRNA aminoacylation step than on the adenylate formation step [14].
• The Cys599 to Tyr mutation affects both the thermal stability of arginyl-tRNA synthetase and the kinetic parameters for arginine in the ATP-PP(i) exchange and tRNA aminoacylation reactions [15].
• We show here that specific substitutions of leucines in the leucine heptad repeats reduced tRNA aminoacylation [16].
• Analysis of these results suggests that the primary defect of the valine substitution is executed at adenylate synthesis while that of the phenylalanine substitution is at both adenylate synthesis and the transition state of tRNA aminoacylation [16].
• Assays of tRNA aminoacylation established the specific attachment of proline to tRNA(Pro) and cysteine to tRNA(Cys) [17].

Gene context of Transfer RNA Aminoacylation

• These results show that p43 and Arc1p are able to facilitate tRNA aminoacylation in vivo even if they do not interact physically with the synthetases [18].
• The tRNA-interacting factor p43 associates with mammalian arginyl-tRNA synthetase but does not modify its tRNA aminoacylation properties [19].
• When incubated with trypsin-modified methionyl-tRNA synthetase (MTST), excess amounts of the dialdehyde derivative of each of these shortened tRNAs (tRNA-C75ox, tRNA-C74ox, tRNA-A73ox, and tRNA-A72ox) abolished both the isotopic [32P]PPi-ATP exchange and the tRNA aminoacylation activities of the enzyme [20].
• Such a strong homology may reveal a new group of genes deriving from a common ancestor, the products of which could be involved in tRNA aminoacylation (tryptophanyl-tRNA synthetase) or translation termination (eRF) [21].
• These results suggest that the region around E292-A293 may be responsible for maintaining the proper conformation of LeuRS required for the tRNA charging activity [22].

References