Universal rules and idiosyncratic features in tRNA identity

Abstract

Correct expression of the genetic code at translation is directly correlated with tRNA identity. This survey describes the molecular signals in tRNAs that trigger specific aminoacylations. For most tRNAs, determinants are located at the two distal extremities: the anticodon loop and the amino acid accepting stem. In a few tRNAs, however, major identity signals are found in the core of the molecule. Identity elements have different strengths, often depend more on k cat effects than on K m effects and exhibit additive, cooperative or anti-cooperative interplay. Most determinants are in direct contact with cognate synthetases, and chemical groups on bases or ribose moieties that make functional interactions have been identified in several systems. Major determinants are conserved in evolution; however, the mechanisms by which they are expressed are species dependent. Recent studies show that alternate identity sets can be recognized by a single synthetase, and emphasize the importance of tRNA architecture and anti-determinants preventing false recognition. Identity rules apply to tRNA-like molecules and to minimalist tRNAs. Knowledge of these rules allows the manipulation of identity elements and engineering of tRNAs with switched, altered or multiple specificities.

Leucyl-tRNA Synthetase from the Hyperthermophilic Bacterium Aquifex aeolicus Recognizes Minihelices

“…In contrast, for tRNAs with identity elements distributed over the whole structure (especially the anticodon position), aminoacylation of the minihelix is generally weak as shown for the IleRS, ValRS, and methionyl-tRNA synthetase (MetRS) systems (20,29,39). A. aeolicus tRNA Leu belongs to the type II tRNA group with an extra variable loop, and its anticodon loop is not necessary for aminoacylation as E. coli tRNA Leu (40,41). However, the aminoacylation level of minihelix Leu is low.…”

ALKBH1-Mediated tRNA Demethylation Regulates Translation

“…eEF1α may preferentially bind m 1 Amethylated tRNA. It is also possible that the methylated tRNAs are preferentially aminoacylated and subsequently recognized by eEF1α, although fully unmodified tRNAs can be readily charged in vitro, and many tRNA synthetases are not known to interact with the tRNA region where m 1 A58 resides (Giegé et al, 1998).…”

BOOL-AN: A method for comparative sequence analysis and phylogenetic reconstruction

“…The validity of this assumption is by no means guaranteed, however. For instance, in vivo and in vitro tRNA identity conversion experiments (Giegé et al, 1998;Hou and Schimmel, 1988;McClain and Foss, 1988;McClain et al, 1991;Normanly et al, 1992) ascertained that functional equality or differences can be revealed irrespective of sequence similarities. It is known that tRNAs that have quite similar sequences may be charged by different amino acids, whereas some isoacceptor tRNAs are quite dissimilar if compared using sequential information.…”

“…It is known that tRNAs that have quite similar sequences may be charged by different amino acids, whereas some isoacceptor tRNAs are quite dissimilar if compared using sequential information. This is because some characteristic structural features (sets of relatively few sequence elements) can be major determinants of the functional identity of tRNAs (Giegé et al, 1998(Giegé et al, , 2007.…”