tRNAs: cellular barcodes for amino acids

Abstract

The role of tRNA in translating the genetic code has received considerable attention over the last 50 years, and we now know in great detail how particular amino acids are specifically selected and brought to the ribosome in response to the corresponding mRNA codon. Over the same period, it has also become increasingly clear that the ribosome is not the only destination to which tRNAs deliver amino acids, with processes ranging from lipid modification to antibiotic biosynthesis all using aminoacyl-tRNAs as substrates. Here we review examples of alternative functions for tRNA beyond translation, which together suggest that the role of tRNA is to deliver amino acids for a variety of processes that includes, but is not limited to, protein synthesis.

Figure 1

Fate of mischarged tRNAs in protein synthesis: Misactivated amino acids can be edited prior to their transfer to the tRNA either in a tRNA independent or dependent fashion (pathways 1 and 2 respectively). Following transfer mischarged aa-tRNA can be edited in cis (pathway 3) or trans (pathway 4) by the aaRS editing site. Free-standing editing factors such as YbaK and AlaXps can also hydrolyze mischarged aa-tRNAs (pathway 4). Mischarged Glu-tRNA^Gln or Asp-tRNA^Asn are converted to Gln-tRNA^Gln or Asn-tRNA^Asn via the transamidase reaction (tRNA-dependent amino acid biosynthesis, pathway 5).

Figure 2

Cellular biosynthetic pathways that utilize aa-tRNAs. Examples are provided in the red shaded boxes of pathways other than protein synthesis, together with the corresponding substrates, that require aa-tRNAs as precursors.

Figure 3

Partitioning of Lys-tRNA^Lys between protein synthesis and lipid remodeling. Lys-tRNA^Lys shows comparable affinities for LysPGS and EF-Tu, allowing aa-tRNAs to potentially enter different biosynthetic pathways simultaneously.