tRNA Biogenesis


During transfer ribonucleic acid (tRNA) biogenesis, tRNA molecules undergo extensive processing before they can fulfill their essential role as the adapter molecule in translation, bringing amino acids into the ribosome for protein synthesis. Many components of the tRNA processing machinery have been identified in a variety of organisms, and a comparison of these shows many common features. However, speciesā€specific features have also been identified, and these present interesting examples of alternative evolutionary pathways and suggest additional interactions between tRNA processing machinery and other cellular processes. An increasing number of mechanisms have been identified that serve to safeguard the tRNA population, either by repair or removal of damaged tRNA species. A picture emerges of a tightly controlled and complex process required for tRNA biogenesis.

Key Concepts:

  • tRNA molecules are heavily processed before their use in translation.

  • Many aspects of tRNA splicing are conserved in multiple domains of life, but there are significant speciesā€specific differences.

  • tRNA modification enzymes exhibit different mechanisms for recognition of specific tRNA species to be modified.

  • Multiple quality control pathways exist that serve to repair and protect the cellular tRNA pool.

Keywords: processing; modification; editing; quality control; splicing; tRNA

Figure 1.

tRNA biogenesis requires multiple processing events. Precursor tRNA transcripts (top) contain 5′‐leader and 3′‐trailer sequences (dark blue) that must be removed before function in protein synthesis, and some tRNA species also contain introns (red) that must be removed by splicing. The 3‐CCA end is added following 3′ end processing in organisms in which the CCA sequence is not genomically encoded. Multiple base and sugar nucleotide modifications (indicated by stars in the mature tRNA molecule) are added in a tRNA sequence and/or species specific manner.

Figure 2.

Divergent pathways for protein enzyme‐dependent tRNA splicing. The first step of tRNA splicing, catalysed by the splicing endonuclease, is common to all organisms in which splicing has been investigated. After this step, two divergent pathways have been identified. The direct ligation pathway shown to occur in extracts derived from vertebrates and archaea is shown on the left; this pathway results in production of a mature tRNA in which the phosphodiester bond linking the 5′‐ and 3′‐half molecules is derived from the 2′–3′ cyclic phosphate generated by the splicing endonuclease. On the right half of the figure, the yeast and plant ligation pathway is shown. The phosphate moiety linking the 5′‐ and 3′‐half molecules in this pathway is derived from the γ‐phosphate of guanosine triphosphateGTP used to activate the 5′‐half molecule, and the 2′‐phosphate must be removed by the action of the 2′‐phosphotransferase. Further metabolism of the nucleotide by‐product produced by the yeast splicing pathway (adenosine diphosphate (ADP)‐ribose‐1″‐2″ cyclic phosphate, Appr>p, red circle) is as indicated.



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Söll D and RajBhandary U (1995) tRNA: Structure, Biosynthesis, and Function. Washington, DC: ASM Press.

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Jackman, Jane E(Dec 2010) tRNA Biogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020894]