Aminoacyl-tRNA

An aminoacyl-tRNA, with the tRNA above the arrow and a generic amino acid below the arrow. Most of the tRNA structure is shown as a simplified, colorful ball-and-stick model; the terminal adenosine and the amino acid are shown as structural formulas. The arrow indicates the ester linkage between the amino acid and tRNA.

Aminoacyl-tRNA (also aa-tRNA or charged tRNA) is tRNA to which its cognate amino acid is chemically bonded (charged). The aa-tRNA, along with particular elongation factors, deliver the amino acid to the ribosome for incorporation into the polypeptide chain that is being produced during translation.

Alone, an amino acid is not the substrate necessary to allow for the formation of peptide bonds within a growing polypeptide chain. Instead, amino acids must be "charged" or aminoacylated with a tRNA to form their respective aa-tRNA.[1] Every amino acid has its own specific aminoacyl-tRNA synthetase, which is utilized to chemically bind to the tRNA that it is specific to, or in other words, "cognate" to. The pairing of a tRNA with its cognate amino acid is crucial, as it ensures that only the particular amino acid matching the anticodon of the tRNA, and in turn matching the codon of the mRNA, is used during protein synthesis.

In order to prevent translational errors, in which the wrong amino acid is incorporated into the polypeptide chain, evolution has provided for proofreading functionalities of aa-tRNA synthetases; these mechanisms ensure the proper pairing of an amino acid to its cognate tRNA.[2] Amino acids that are misacylated with the proper tRNA substrate undergo hydrolysis through the deacylation mechanisms possessed by aa-tRNA synthetases.[3]

Due to the degeneracy of the genetic code, multiple tRNAs will have the same amino acid but different anticodons. These different tRNAs are called isoacceptors. Under certain circumstances, non-cognate amino acids will be charged, resulting in mischarged or misaminoacylated tRNA. These mischarged tRNAs must be hydrolyzed in order to prevent incorrect protein synthesis.

While aa-tRNA serves primarily as the intermediate link between the mRNA coding strand and the encoded polypeptide chain during protein synthesis, it is also found that aa-tRNA have functions in several other biosynthetic pathways. aa-tRNAs are found to function as substrates in biosynthetic pathways for cell walls, antibiotics, lipids, and protein degradation.

It is understood that aa-tRNAs may function as donors of amino acids necessary for the modification of lipids and the biosynthesis of antibiotics. For example, microbial biosynthetic gene clusters may utilize aa-tRNAs in the synthesis of non-ribosomal peptides and other amino acid-containing metabolites.[4]

  1. ^ Peacock JR, Walvoord RR, Chang AY, Kozlowski MC, Gamper H, Hou YM (June 2014). "Amino acid-dependent stability of the acyl linkage in aminoacyl-tRNA". RNA. 20 (6): 758–64. doi:10.1261/rna.044123.113. PMC 4024630. PMID 24751649.
  2. ^ Kelly P, Ibba M (January 2018). "Aminoacyl-tRNA Quality Control Provides a Speedy Solution to Discriminate Right from Wrong". Journal of Molecular Biology. 430 (1): 17–19. doi:10.1016/j.jmb.2017.10.025. PMID 29111345.
  3. ^ Francklyn CS, Mullen P (April 2019). "Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics". The Journal of Biological Chemistry. 294 (14): 5365–5385. doi:10.1074/jbc.REV118.002956. PMC 6462538. PMID 30670594.
  4. ^ Ulrich EC, van der Donk WA (December 2016). "Cameo appearances of aminoacyl-tRNA in natural product biosynthesis". Current Opinion in Chemical Biology. 35: 29–36. doi:10.1016/j.cbpa.2016.08.018. PMC 5161580. PMID 27599269.