Relaxation of a transfer RNA specificity by removal of modified nucleotides

Abstract

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 we consider whether the base modifications commonly found in tRNAs contribute to their identity. Although unmodified tRNA(Asp) is charged with aspartate as efficiently as the modified native tRNA, it is mischarged with arginine with considerably increased efficiency. Our results indicate that post-transcriptional modification of tRNAs introduces structural 'anti-determinants', restricting the efficiency with which the tRNAs are charged with inappropriate amino acids.

LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure

“…WT and variant LARS2 were expressed and purified as previously described (Yao et al 2003). The sequence of Escherichia coli tRNA 5 Leu (UAA) was cloned, transcribed, and purified according to established procedures (Perret et al 1990). In vitro leucylation of the tRNA Leu transcript was performed in the presence of 30 mM L-[ 14 C]leucine at 37 C as previously described (Sohm et al 2003).…”

Primary sequence and post‐transcriptional modification pattern of an unusual mitochondrial tRNAMet from Tetrahymena pyriformis

“…The 3'-CCA sequence is a universal feature of all tRNAs and is important in many aspects of tRNA function [22], including aminoacylation [23,24] and interaction with large subunit rRNA [25]. This tRNA also contains several modified nucleosides that are highly conserved among tRNAs and are thought to be important for tRNA structure and function [26][27][28][29][30][31][32][33].…”

Identity elements of Thermus thermophilus tRNAThr

“…A small set of nucleotides of tRNA, which often includes anticodon nucleotides and the discriminator base at position 73, are major identity elements governing specific aminoacylation [4][5][6][7]. In addition to positive recognition by cognate aminoacyl-tRNA synthetase, negative elements prevent a tRNA from being recognized by a non-cognate synthetase [8,9]. Recently, systematic studies of recognition sets in several organisms have enabled comparisons of the tRNA recognition between prokaryotes and eukaryotes, which have indicated not only similarities, but also differences [10][11][12][13][14][15][16][17][18].…”