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PubMed1998

A cognate tRNA specific conformational change in glutaminyl-tRNA synthetase and its implication for specificity.

Conformational changes that occur upon substrate binding are known to play crucial roles in the recognition and specific aminoacylation of cognate tRNA by glutaminyl-tRNA synthetase. In a previous study we had shown that glutaminyl-tRNA synthetase labeled selectively in a nonessential sulfhydryl residue by an environment sensitive probe, acrylodan, monitors many of the conformational changes that occur upon substrate binding. In this article we have shown that the conformational change that occurs upon tRNA(Gln) binding to glnRS/ATP complex is absent in a noncognate tRNA tRNA(Glu)-glnRS/ATP complex. CD spectroscopy indicates that this cognate tRNA(Gln)-induced conformational change may involve only a small change in secondary structure. The Van't Hoff plot of cognate and noncognate tRNA binding in the presence of ATP is similar, suggesting similar modes of interaction. It was concluded that the cognate tRNA induces a local conformational change in the synthetase that may be one of the critical elements that causes enhanced aminoacylation of the cognate tRNA over the noncognate ones.

2-Naphthylamine↗
PubMed1993

Two acidic residues of Escherichia coli methionyl-tRNA synthetase act as negative discriminants towards the binding of non-cognate tRNA anticodons.

Escherichia coli methionyl-tRNA synthetase recognizes its cognate tRNAs according to the sequence of the CAU anticodon. In order to identify residues of methionyl-tRNA synthetase involved in tRNA anticodon recognition, enzyme variants created by cassette mutagenesis were genetically screened for their acquired ability to charge tRNA(mMet) derivatives with an ochre or an amber anticodon and, consequently, to cause the suppression of a stop codon in an indicator gene. The selected enzymes are called suppressors. Mutations were firstly directed towards the region of the synthetase encompassing residues 451 to 467. Several dozens of suppressor enzymes were compared. Statistical analysis of the mutations suggested that the substitution of an Asp side-chain at position 456 was sufficient to render possible the charging of the ochre or amber suppressor tRNAs. Point mutants at this position were therefore constructed. Their behaviour demonstrated that various tRNA(Met) derivatives having a non-Met anticodon could be aminoacylated in vitro provided only that the side-chain of residue 456 was no longer acidic. In turn, the Asp456 residue is not essential to the CAU anticodon recognition, since its substitution does not impair the aminoacylation of wild-type tRNA(Met). The analysis was enlarged to a second region from residue 437 to residue 454. The mutagenesis highlighted two other positions, one of which, Asn452, appeared involved in wild-type tRNA(Met) binding. The second position, Asp449, plays a role very similar to that of Asp456. It is concluded that both Asp449 and 456 behave as "antideterminants", contributing together to the rejection by the enzyme of tRNAs carrying non-Met anticodons. Finally, it is shown that the activities of some particular methionyl-tRNA synthetase variants, which have been made indifferent to the sequence of the anticodon of a tRNA(Met), are tightly dependent on the presence of the nucleotide determinants specific to the acceptor stem of tRNA(Met).

Acylation↗
PubMed2000

The free yeast aspartyl-tRNA synthetase differs from the tRNA(Asp)-complexed enzyme by structural changes in the catalytic site, hinge region, and anticodon-binding domain.

Aminoacyl-tRNA synthetases catalyze the specific charging of amino acid residues on tRNAs. Accurate recognition of a tRNA by its synthetase is achieved through sequence and structural signalling. It has been shown that tRNAs undergo large conformational changes upon binding to enzymes, but little is known about the conformational rearrangements in tRNA-bound synthetases. To address this issue the crystal structure of the dimeric class II aspartyl-tRNA synthetase (AspRS) from yeast was solved in its free form and compared to that of the protein associated to the cognate tRNA(Asp). The use of an enzyme truncated in N terminus improved the crystal quality and allowed us to solve and refine the structure of free AspRS at 2.3 A resolution. For the first time, snapshots are available for the different macromolecular states belonging to the same tRNA aminoacylation system, comprising the free forms for tRNA and enzyme, and their complex. Overall, the synthetase is less affected by the association than the tRNA, although significant local changes occur. They concern a rotation of the anticodon binding domain and a movement in the hinge region which connects the anticodon binding and active-site domains in the AspRS subunit. The most dramatic differences are observed in two evolutionary conserved loops. Both are in the neighborhood of the catalytic site and are of importance for ligand binding. The combination of this structural analysis with mutagenesis and enzymology data points to a tRNA binding process that starts by a recognition event between the tRNA anticodon loop and the synthetase anticodon binding module.

Anticodon↗
PubMed1992

Mammalian prolyl-tRNA synthetase corresponds to the approximately 150 kDa subunit of the high-M(r) aminoacyl-tRNA synthetase complex.

The high-M(r) aminoacyl-tRNA synthetase complex previously purified from sheep liver differed from those isolated from several other mammalian sources by the absence of prolyl-tRNA synthetase activity and the presence of glutamyl tRNA synthetase as a polypeptide of 85 kDa instead of 150 kDa. Using a milder extraction procedure that minimizes proteolysis, we now report the isolation of a sheep liver complex that contains both prolyl-tRNA synthetase activity and the 150-kDa polypeptide. The correspondence between prolyl-tRNA synthetase and the 150-kDa polypeptide, inferred from the results of several approaches reported in this study, was further demonstrated by showing that antibodies to a free form of sheep liver prolyl-tRNA synthetase generated by endogenous proteolysis, specifically reacted with the 150-kDa components of the complexes from sheep and rabbit, but failed to react with the previously purified complex from sheep that contained neither prolyl-tRNA synthetases activity nor the 150-kDa component. Moreover, we show that the 150-kDa polypeptide is also recognized by antibodies to the 85-kDa polypeptide previously assigned to glutamyl-tRNA synthetase. The possibility that the largest subunit of the mammalian high-M(r) complexes may be a bifunctional protein encoding both glutamyl- and prolyl-tRNA synthetase activities is considered and discussed in light of the recently published sequence of the corresponding polypeptide from HeLa cells. In accordance with this prediction, we show that the amino acid sequence of the carboxyl-terminal moiety of this bifunctional polypeptide shows significant similarity to the sequence of prolyl-tRNA synthetase from Escherichia coli.

Amino Acid Sequence↗
PubMed1993

Selectivity and specificity in the recognition of tRNA by E coli glutaminyl-tRNA synthetase.

The specific recognition by Escherichia coli glutaminyl-tRNA synthetase (GlnRS) of tRNA(Gln) is mediated by extensive protein:RNA contacts and changes in the conformation of tRNA(Gln) when complexed with GlnRS. In vivo accuracy of aminoacylation depends on two factors: competition between synthetases, and the context and recognition of identity elements in the tRNA. The structure of the tRNA(Gln):GlnRS complex supports studies from amber and opal suppressor tRNAs, complemented by in vitro aminoacylation of the mutated tRNA transcripts, that the glutamine identity elements are located in the anticodon and acceptor stem of tRNA(Gln). Recognition of individual functional groups in tRNA, for example the 2-amino group of guanosine, is also evident from the result with inosine-substituted tRNAs. Communication between anticodon and acceptor stem recognition is indicated by mutants in GlnRS isolated by genetic selection with opal suppressor tRNAs which are altered in interactions with the inside of the L-shaped tRNA. We have also used genetic selection to obtain mutants of GlnRS altered in acceptor stem recognition with relaxed specificity for amber suppressor tRNAs, and a more extensive mutational analysis shows the importance of the acceptor binding domain to accurate recognition of tRNA.

Amino Acyl-tRNA Synthetases↗
PubMed1996

Yeast tRNA(Met) recognition by methionyl-tRNA synthetase requires determinants from the primary, secondary and tertiary structure: a review.

The primordial role of the CAU anticodon in methionine identity of the tRNA has been established by others nearly a decade ago in Escherichia coli and yeast tRNA(Met). We show here that the CAU triplet alone is unable to confer methionine acceptance to a tRNA. This requires the contribution of the discriminatory base A73 and the non-anticodon bases of the anticodon loop. To better understand the functional communication between the anticodon and the active site, we analysed the binding and aminoacylation of tRNA(Met) based anticodon and acceptor-stem minihelices and of tRNA(Met) chimeras where the central core region of yeast tRNA(Met) is replaced by that of unusual mitochondrial forms lacking either a D-stem or a T-stem. These studies suggest that the high selectivity of the anticodon bases in tRNA(Met) implies the L-conformation of the tRNA and the presence of a D-stem. The importance of a L-structure for recognition of tRNA(Met) was also deduced from mutations of tertiary interactions known to play a general role in tRNA(Met) folding.

Amino Acid Sequence↗
PubMed1999

Chloride affects the interaction between tyrosyl-tRNA synthetase and tRNA.

The physiological concentration of free magnesium in Escherichia coli cells is about 1 mM, and there is almost no chloride in the cell. When the aminoacylation of tRNA by tyrosyl-tRNA synthetase was assayed at 1 mM free Mg2+, chloride (and sulphate) ions inhibited the reaction but acetate at the same concentration (< 200 mM) was not inhibitory. When the magnesium concentration was increased to 10 mM there was almost no chloride inhibition any more. Chloride strengthened the PPi inhibition, the Ki(app)(PPi) values at 1 mM free Mg2+ were 140, 120, and 56 microM at 0, 50 and 150 mM KCl, respectively. Chloride weakened the AMP inhibition, the corresponding values for Ki(app)(AMP) were 0.35, 0.5, and 0.9 mM. The value of Km(app)(tRNA(Tyr)) was clearly increased by chloride, being 22, 37, 93, and 240 nM at 0, 50, 100, and 150 mM KCl, respectively. Best-fit analyses of the PPi inhibition, AMP inhibition and Km(app)(tRNA) assays were accomplished using total rate equations. The analysis showed that the only kinetic events which are obligatory to explain the chloride effects are a weakened binding of Mg2+ to the tRNA before the transfer reaction and a weakened binding of Mg2+ to the Tyr-tRNA-enzyme complex after the transfer reaction. The dissociation constants for the former were 0.11, 0.3, and 2.8 mM and for the latter 0.6, 2.5, and 13 mM at 0, 50 and 150 mM KCl, respectively. Mg2+ is required for the reactive conformation of tRNA in the transfer reaction but chloride weakens its formation. After the transfer reaction the dissociation of Mg2+ from the aa-tRNA-enzyme complex enhances the dissociation of the aa-tRNA from the enzyme. The kinetics and the chloride effect were similar in the tyrosyl-tRNA synthetases from both Bacillus stearothermophilus and E. coli.

Chlorides↗
PubMed1998

The RNA sequence context defines the mechanistic routes by which yeast arginyl-tRNA synthetase charges tRNA.

Arginylation of tRNA transcripts by yeast arginyl-tRNA synthetase can be triggered by two alternate recognition sets in anticodon loops: C35 and U36 or G36 in tRNA(Arg) and C36 and G37 in tRNA(Asp) (Sissler M, Giegé R, Florentz C, 1996, EMBO J 15:5069-5076). Kinetic studies on tRNA variants were done to explore the mechanisms by which these sets are expressed. Although the synthetase interacts in a similar manner with tRNA(Arg) and tRNA(Asp), the details of the interaction patterns are idiosyncratic, especially in anticodon loops (Sissler M, Eriani G, Martin F, Giegé R, Florentz C, 1997, Nucleic Acids Res 25:4899-4906). Exchange of individual recognition elements between arginine and aspartate tRNA frameworks strongly blocks arginylation of the mutated tRNAs, whereas full exchange of the recognition sets leads to efficient arginine acceptance of the transplanted tRNAs. Unpredictably, the similar catalytic efficiencies of native and transplanted tRNAs originate from different k(cat) and Km combinations. A closer analysis reveals that efficient arginylation results from strong anticooperative effects between individual recognition elements. Nonrecognition nucleotides as well as the tRNA architecture are additional factors that tune efficiency. Altogether, arginyl-tRNA synthetase is able to utilize different context-dependent mechanistic routes to be activated. This confers biological advantages to the arginine aminoacylation system and sheds light on its evolutionary relationship with the aspartate system.

Anticodon↗
PubMed1995

Residues in a class I tRNA synthetase which determine selectivity of amino acid recognition in the context of tRNA.

Certain aminoacyl-tRNA synthetases discriminate between closely similar amino acids by hydrolytic editing reactions in the presence of their cognate tRNA. An example is the class I isoleucyl-tRNA synthetase. We recently showed that a mutation which eliminates discrimination between isoleucine (Ile) and valine (Val) in the initial amino acid binding and activation steps had little effect on the hydrolytic editing of activated valine in the presence of isoleucine tRNA (tRNA(Ile)). The results showed that initial amino acid binding and discrimination are functionally independent of tRNA-dependent amino acid discrimination. In this work, we cross-linked (to isoleucyl-tRNA synthetase) a reactive analog of valine misacylated onto tRNA(Ile). Mutation of specific residues within a peptide segment identified by the cross-linking analysis severely affected discrimination of Val-tRNA(Ile) versus Ile-tRNA(Ile). The mutationally sensitive residues are part of an insertion into the catalytic domain and are themselves completely conserved among all known prokaryotic and eukaryotic sequences of the enzyme.

Amino Acid Sequence↗
PubMed1994

Escherichia coli proline tRNA synthetase is sensitive to changes in the core region of tRNA(Pro).

To investigate the relationship between tRNA conformation and specific recognition by aminoacyl-tRNA synthetases, a full-length tRNA molecule was assembled by annealing together two oligonucleotides representing fragments of Escherichia coli tRNA(Pro). A shorter chemically synthesized 5'-fragment (7-18 nucleotides) was combined with an in vitro transcribed 3'-fragment (59 nucleotides). Despite a break in the phosphodiester backbone between nucleotides U17a and G18, this tRNA molecule was an efficient substrate for class II Escherichia coli proline tRNA synthetase. While the deletion of three D-loop nucleotides (U17a, U17, and C16) was tolerated, removal of G15 and A14 significantly reduced aminoacylation efficiency. Hybrid DNA-RNA "annealed" substrates were also prepared and assayed for aminoacylation. Native gel electrophoresis was used to compare the global folding of the various substrates tested. The results of these studies suggest that proline tRNA synthetase is sensitive to changes in the core region of tRNA(Pro) through which information required for efficient aminoacylation may be transmitted. In particular, nucleotides in the D-loop and backbone functional groups in the D-stem appear to be critical for maintaining a tRNA structure that is optimal for recognition by proline tRNA synthetase in vitro.

Amino Acyl-tRNA Synthetases↗
PubMed2002

Discrimination of tRNA(Leu) isoacceptors by the mutants of Escherichia coli leucyl-tRNA synthetase in editing.

Leucyl-tRNA synthetase (LeuRS), one of the class Ia aminoacyl-tRNA synthetases, joins Leu to tRNA(Leu) and excludes noncognate amino acids in protein synthesis. In this study, Escherichia coli LeuRS mutants at amino acid E292, which was located in the connective polypeptide 1 insertion region, were synthesized. Although mutated LeuRS showed little change in structure compared with wild-type LeuRS, the mutants were impaired in activity to varying extents. It was also showed that mutations did not affect the adenylation reaction. However, mutated LeuRS can mischarge tRNA(Leu) isoacceptors tRN or tRN with isoleucine to different extents. Isoleucylation of tRN was more than that of tRN. The mutant LeuRS-E292S, which was picked out as an example for the investigation of the relationship between tRNA(Leu) isoacceptors and editing function, can discriminate the Watson-Crick base pair of the first base pair of tRNA(Leu) from the wobble base pair. The tRNA(Leu) with the Watson-Crick base pair may result in more isoleucylated product than that with the wobble base pair. The same phenomenon happened to another mutant, LeuRS-A293D. It seems that the flexibility of the first base pair affects the editing reaction of LeuRS. The results indicate that the flexibility of the first base pair of tRNA(Leu) may probably affect the mischarged 3'-end of tRNA(Leu) shuttling from synthetic site to editing site and that the transferred acceptor arm of tRNA(Leu) may interact with LeuRS in the region around E292.

Acylation↗
PubMed2006

The nondiscriminating aspartyl-tRNA synthetase from Helicobacter pylori: anticodon-binding domain mutations that impact tRNA specificity and heterologous toxicity.

Divergent tRNA substrate recognition patterns distinguish the two distinct forms of aspartyl-tRNA synthetase (AspRS) that exist in different bacteria. In some cases, a canonical, discriminating AspRS (D-AspRS) specifically generates Asp-tRNA(Asp) and usually coexists with asparaginyl-tRNA synthetase (AsnRS). In other bacteria, particularly those that lack AsnRS, AspRS is nondiscriminating (ND-AspRS) and generates both Asp-tRNA(Asp) and the noncanonical, misacylated Asp-tRNA(Asn); this misacylated tRNA is subsequently repaired by the glutamine-dependent Asp-tRNA(Asn)/Glu-tRNA(Gln) amidotransferase (Asp/Glu-Adt). The molecular features that distinguish the closely related bacterial D-AspRS and ND-AspRS are not well-understood. Here, we report the first characterization of the ND-AspRS from the human pathogen Helicobacter pylori (H. pylori or Hp). This enzyme is toxic when heterologously overexpressed in Escherichia coli. This toxicity is rescued upon coexpression of the Hp Asp/Glu-Adt, indicating that Hp Asp/Glu-Adt can utilize E. coli Asp-tRNA(Asn) as a substrate. Finally, mutations in the anticodon-binding domain of Hp ND-AspRS reduce this enzyme's ability to misacylate tRNA(Asn), in a manner that correlates with the toxicity of the enzyme in E. coli.

Amino Acid Sequence↗
PubMed1997

Zinc-dependent tRNA binding by a peptide element within a tRNA synthetase.

The class I aminoacyl-tRNA synthetases are defined by an N-terminal nucleotide binding fold that contains the active site for adenylate synthesis. Insertions and additions of idiosyncratic RNA binding elements that facilitate docking of the L-shaped tRNA structure are superimposed onto this basic fold. These RNA binding elements are imagined to have been acquired during the evolution and development of the modern genetic code. The monomeric Escherichia coli isoleucyl-tRNA synthetase has a zinc-containing peptide at its C terminus. Removal of the zinc-containing peptide was shown previously to create a shortened enzyme with activity for adenylate synthesis but no detectable binding to tRNA(Ile). We show here that the isolated zinc-containing peptide binds to tRNA with relatively low affinity. This binding is not tRNA-specific but shows a strict requirement for zinc. In contrast, the zinc-containing peptide conferred specific and high-affinity binding when combined with the shortened enzyme. Thus, when combined with another protein, a nonspecific tRNA binding peptide is essential for formation of a high-affinity and specific tRNA binding site. These results demonstrate the feasibility of the idea that noncovalent complexes of general RNA-binding peptides with a domain for adenylate synthesis were precursors to modern tRNA synthetases. In addition, the results offer the first direct evidence of a role for zinc in the tRNA-binding activity of one of these peptide elements.

Amino Acid Sequence↗
PubMed2001

The N-terminal domain of mammalian Lysyl-tRNA synthetase is a functional tRNA-binding domain.

Lysyl-tRNA synthetase from higher eukaryotes possesses a lysine-rich N-terminal polypeptide extension appended to a classical prokaryotic-like LysRS domain. Band shift analysis showed that this extra domain provides LysRS with nonspecific tRNA binding properties. A N-terminally truncated derivative of LysRS, LysRS-DeltaN, displayed a 100-fold lower apparent affinity for tRNA(3)Lys and a 3-fold increase in K(m) for tRNA(3)Lys in the aminoacylation reaction, as compared with the native enzyme. The isolated N-domain of LysRS also displayed weak affinity for tRNA, suggesting that the catalytic and N-domains of LysRS act synergistically to provide a high affinity binding site for tRNA. A more detailed analysis revealed that LysRS binds and specifically aminoacylates an RNA minihelix mimicking the amino acid acceptor stem-loop structure of tRNA(3)Lys, whereas LysRS-DeltaN did not. As a consequence, merging an additional RNA-binding domain into a bacterial-like LysRS increases the catalytic efficiency of the enzyme, especially at the low concentration of deacylated tRNA prevailing in vivo. Our results provide new insights into tRNA(Lys) channeling in eukaryotic cells and shed new light on the possible requirement of native LysRS for triggering tRNA(3)Lys packaging into human immunodeficiency virus, type 1 viral particles.

Amino Acid Sequence↗
PubMed2002

Yeast tRNA(Asp) charging accuracy is threatened by the N-terminal extension of aspartyl-tRNA synthetase.

This study evaluates the role of the N-terminal extension from yeast aspartyl-tRNA synthetase in tRNA aspartylation. The presence of an RNA-binding motif in this extension, conserved in eukaryotic class IIb aminoacyl-tRNA synthetases, provides nonspecific tRNA binding properties to this enzyme. Here, it is assumed that the additional contacts the 70 amino acid-long appendix of aspartyl-tRNA synthetase makes with tRNA could be important in expression of aspartate identity in yeast. Using in vitro transcripts mutated at identity positions, it is demonstrated that the extension grants better aminoacylation efficiency but reduced specificity to the synthetase, increasing considerably the risk of noncognate tRNA mischarging. Yeast tRNA(Glu(UUC)) and tRNA(Asn(GUU)) were identified as the most easily mischarged tRNA species. Both have a G at the discriminator position, and their anticodon differs only by one change from the GUC aspartate anticodon.

Amino Acid Motifs↗
PubMed2002

tRNA(Lys3): the primer tRNA for reverse transcription in HIV-1.

During the assembly of HIV-1, tRNA(Lys) isoacceptors are selectively packaged into the virion, and one of these, tRNA(Lys3), is annealed to the viral RNA genome where it acts to prime the reverse transcriptase (RT)-catalyzed synthesis of viral DNA. We review herein what is known about the selective packaging and annealing of primer tRNA(Lys3). Current evidence suggests that a complex of two major precursor viral proteins, Pr55gag and Pr160(gag-pol), interact with a tRNA(Lys)/lysyl-tRNA synthetase (LysRS) complex during viral assembly, with Pr55gag interacting with both LysRS and Pr160(gag-pol), and RT sequences within Pr160(gag-pol) binding to tRNA(Lys). LysRS appears to target the tRNA(Lys) isoacceptors for incorporation into HIV-1. In the virion, the 3' terminal 18 nucleotides of tRNA(Lys3) anneals to an 18-nucleotide sequence at the 5' terminal region of viral RNA termed the primer binding site (PBS). Evidence is presented that other regions on the tRNA(Lys3) also anneal with other regions in viral RNA upstream of the PBS, resulting in a destabilized tRNA(Lys3) structure. Both viral and tRNA(Lys3) regions need to be denatured to establish annealing, and the roles of both viral and cellular proteins in this process are discussed.

Base Sequence↗
PubMed2006

Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity.

Aminoacyl-tRNA synthetases (aaRSs) are a family of enzymes responsible for the covalent link of amino acids to their cognate tRNAs. The selectivity and species-specificity in the recognitions of both amino acid and tRNA by aaRSs play a vital role in maintaining the fidelity of protein synthesis. We report here the first crystal structure of human tryptophanyl-tRNA synthetase (hTrpRS) in complex with tRNA(Trp) and Trp which, together with biochemical data, reveals the molecular basis of a novel tRNA binding and recognition mechanism. hTrpRS recognizes the tRNA acceptor arm from the major groove; however, the 3' end CCA of the tRNA makes a sharp turn to bind at the active site with a deformed conformation. The discriminator base A73 is specifically recognized by an alpha-helix of the unique N-terminal domain and the anticodon loop by an alpha-helix insertion of the C-terminal domain. The N-terminal domain appears to be involved in Trp activation, but not essential for tRNA binding and acylation. Structural and sequence comparisons suggest that this novel tRNA binding and recognition mechanism is very likely shared by other archaeal and eukaryotic TrpRSs, but not by bacterial TrpRSs. Our findings provide insights into the molecular basis of tRNA specificity and species-specificity.

Amino Acid Sequence↗
PubMed1988

Accuracy of in vivo aminoacylation requires proper balance of tRNA and aminoacyl-tRNA synthetase.

The fidelity of protein biosynthesis in any cell rests on the accuracy of aminoacylation of tRNA. The exquisite specificity of this reaction is critically dependent on the correct recognition of tRNA by aminoacyl-tRNA synthetases. It is shown here that the relative concentrations of a tRNA and its cognate aminoacyl-tRNA synthetase are normally well balanced and crucial for maintenance of accurate aminoacylation. When Escherichia coli Gln-tRNA synthetase is overproduced in vivo, it incorrectly acylates the supF amber suppressor tRNA(Tyr) with Gln. This effect is abolished when the intracellular concentration of the cognate tRNA(Gln2) is also elevate. These data indicate that the presence of aminoacyl-tRNA synthetase and the cognate tRNAs in complexed form, which requires the proper balance of the two macromolecules, is critical in maintaining the fidelity of protein biosynthesis. Thus, limits exist on the relative levels of tRNAs and aminoacyl-tRNA synthetases within a cell.

Amino Acyl-tRNA Synthetases↗