Transiently misacylated tRNA is a primer for editing of misactivated adenylates by class I aminoacyl-tRNA synthetases.
The genetic code depends on amino acid fine structure discrimination by aminoacyl-tRNA synthetases. For isoleucyl- (IleRS) and valyl-tRNA synthetases (ValRS), reactions that hydrolyze misactivated noncognate amino acids help to achieve high accuracy in aminoacylation. Two editing pathways contribute to aminoacylation fidelity: pretransfer and post-transfer. In pretransfer editing, the misactivated amino acid is hydrolyzed as an aminoacyl adenylate, while in post-transfer editing a misacylated tRNA is deacylated. Both reactions are dependent on a tRNA cofactor and require translocation to a site located approximately 30 A from the site of amino acid activation. Using a series of 3'-end modified tRNAs that are deficient in either aminoacylation, deacylation, or both, total editing (the sum of pre- and post-transfer editing) was shown to require both aminoacylation and deacylation activities. These and additional results with IleRS are consistent with a post-transfer deacylation event initiating formation of an editing-active enzyme/tRNA complex. In this state, the primed complex processively edits misactivated valyl-adenylate via the pretransfer route. Thus, misacylated tRNA is an obligatory intermediate for editing by either pathway.
Nordin
Brian E
BE
The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Schimmel
Paul
P
D024509:3' Flanking Region; D000215:Acylation; D000227:Adenine Nucleotides / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000737:chemistry; D006868:Hydrolysis; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry*; D017393:RNA Editing; D012329:RNA, Bacterial / Q000737:chemistry; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry*; D013379:Substrate Specificity; D014637:Valine-tRNA Ligase / Q000737:chemistry*
D000227:Adenine Nucleotides; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012346:RNA, Transfer, Amino Acyl; D000251:Adenosine Triphosphatases; D007533:Isoleucine-tRNA Ligase; D014637:Valine-tRNA Ligase