Methionyl-tRNA

An obvious extension of studies aimed at investigating the localization of translation initiation factors is an analysis of the localization of specific RNA species. For instance, with respect to the localization of eIF2, the localization of the initiator methionyl tRNA is an important consideration. 

Hinnebusch, A. (2000). Mechanism and Regulation of Initiator Methionyl-tRNA Binding to Ribosomes. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 

Hinnebusch, A. G. (2000). Mechanism and regulation of initiator methionyl-tRNA binding to ribosomes. In Translational Control of Gene Expression (N. Sonenberg,... 

Ferguson, B., and Yang, D. (1986) Localization of noncovalently bound ethidium in free and methionyl-tRNA synthetase bound tRNA(fMet) by singlet - singlet energy transfer. Biochemistry 25, 5298. 

This enzyme [EC 2.1.2.9] catalyzes the reaction of 10-formyltetrahydrofolate with L-methionyl-tRNA and water to produce tetrahydrofolate and iV-formylmethio-nyl-tRNA. 

This enzyme [EC 6.1.1.10], also known as methio-nineitRNA ligase, catalyzes the reaction of methionine with tRNA and ATP to produce methionyl-tRNA , AMP, and pyrophosphate (or, diphosphate). See also... 

METHIONYL-tRNA SYNTHETASE METHIONYL-tRNA FORMYLTRANSFERASE METHIONYL-tRNA SYNTHETASE AMINO-ACYL tRNA SYNTHETASES Method of continuous variation,... 

METHIONINE ADENOSYLTRANSFERASE METHIONYL-tRNA SYNTHETASE NAD SYNTHETASE... 

Complementary, antiparallel bindinc of the anticodon for methionyl-tRNA (CAU) to the mRNA codon for methionine (AUG). 

Discrimination between some pairs of tRNAs depends entirely on the anticodon sequence. For example, tRNAMet contains the anticodon CAU. That for a minor tRNAIle is the same except that the cytosine has been posttranscriptionally modified by covalent linkage of a molecule of lysine via its e-amino group to C2 of the cytosine. The latter base (Iysidine) is correctly recognized by E. coli isoleucyl-tRNA synthetase but, if the cytosine is unmodified, it is aminoacylated by methionyl-tRNA synthetase.192 In most instances the acceptor specificity, or tRNA identity, is not determined solely by the anticodon sequence. Thus, when a methionine initiator tRNA was modified to contain a tryptophan anticodon, it was only partially charged with tryptophan in vivo. However, when A73 of the methionine tRNA was also converted to G73, only tryptophan was inserted.193 Nucleotide 73 (Fig. 

A similar editing process prevents isoleucyl-, leucyl-, and methionyl-tRNA synthetases from attaching L-homocysteine to tRNAs 260-263 In this case, instead of hydrolysis the editing site catalyzes conversion of the homocysteinyl-adenylate into homocysteine lactone. Naturally occurring mutations in tRNA molecules can sometimes have serious consequences. For example, a human mutation is responsible for a fragile mitochondrial isoleucine tRNA and serious cardiomyopathy and opthalmophegia (see also Box 18-B).263a... 

In E. coli polypeptide chains are always initiated with the amino acid N-formylmethionine. Some bacteria can apparently live without the ability to formylate methionyl-tRNA,290 but most eubacteria as well as mitochondria and chloroplasts use formyl-methionine for initiation. In a few cases, both among bacteria and eukaryotes, initiation can sometimes occur with other amino acids 291 The first step is the alignment of the proper initiation codon correctly on... 

The methionyl-tRNA synthetase edits Tnisactivated homocysteine before the transfer to tRNAMet. The homocysteinyl adenylate complex is rapidly decomposed in the absence of tRNA. The reaction is, however, idiosyncratic, in that it invokes the cyclization of the intermediate to give the thiolactone.12... 

A unique methionyl-tRNA binds to the initiation codon on all messages. 

Initiation factors contribute to the ribosome complex with the messenger RNA and the initiator methionyl-tRNA. Elongation factors assist the binding of all the other tRNAs and the translocation reaction that must occur after each peptide bond is made. Termination factors recognize a stop signal and lead to the termination of polypeptide synthesis and the release of the polypeptide chain and the messenger from the ribosome. 

Biosynthetic processes Elongation of RNA or DNA chains Other synthetic routes RNA polymerase I DNA polymerase Poly(ADP-ribose)polymerase Carbamoyl phosphate synthetase Anthranilate synthase-phosphoribosyl transferase Glycogen synthetase Methionyl-tRNA synthetase ATP phosphoribosyl transferase Zn2+... 

Both prokaryotes and eukaryotes initiate protein synthesis with a specialized methionyl-tRNA in response to an AUG initiation codon. Eukaryotes, however, use an initiator met—tRNAmeti—that is not formylated. Recognition of the initiator AUG is also different. Only one coding sequence exists per eukaryotic mRNA, and eukaryotic mRNAs are capped. Initiation, therefore, uses a specialized capbinding initiation factor to position the mRNA on the small riboso-mal subunit. Usually, the first AUG after the cap (that is, 3 to it) is used for initiation. 

Schmitt, E., Blanquet, S., and Mechulam, Y. (1996). Structure of crystalline Escherichia colt methionyl-tRNA(f)Met formyltransferase comparison with glycinamide ribonucleotide formyltransferase. EMBO J., 15, 4749-4758. 

Burnell, J.N. 1981. Methionyl-tRNA synthetase from Phaseolus aureus purification and properties. Plant Physiol. 67, 316-324. 

Question Is there any special feature of methionyl-tRNA, in addition to the presence of an anticodon for AUG, that is required for its participation in initiation of translation ... 

Jarvest, R.L. et al. 2002. Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens. J. Med. Chem. 45, 1959-1962. 

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