tRNA Biogenesis

Abstract

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.

close

References

Abelson J, Trotta CR and Li H (1998) tRNA splicing. [Review] [43 refs]. Journal of Biological Chemistry 273: 12685–12688.

Alexandrov A, Chernyakov I, Gu W et al. (2006) Rapid tRNA decay can result from lack of nonessential modifications. Molecular Cell 21: 87–96.

Alfonzo JD, Blanc V, Estevez AM, Rubio MA and Simpson L (1999) C to U editing of the anticodon of imported mitochondrial tRNA(Trp) allows decoding of the UGA stop codon in Leishmania tarentolae. EMBO Journal 18: 7056–7062.

Antes T, Costandy H, Mahendran R, Spottswood M and Miller D (1998) Insertional editing of mitochondrial tRNAs of Physarum polycephalum and Didymium nigripes. Molecular and Cellular Biology 18: 7521–7527.

Bullerwell CE and Gray MW (2005) In vitro characterization of a tRNA editing activity in the mitochondria of Spizellomyces punctatus, a Chytridiomycete fungus. Journal of Biological Chemistry 280: 2463–2470.

Chernyakov I, Whipple JM, Kotelawala L, Grayhack EJ and Phizicky EM (2008) Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5′‐3′ exonucleases Rat1 and Xrn1. Genes & Development 22: 1369–1380.

Culver GM, McCraith SM, Zillmann M et al. (1993) An NAD derivative produced during transfer RNA splicing: ADP‐ribose 1″‐2″ cyclic phosphate. Science 261: 206–208.

Czerwoniec A, Dunin‐Horkawicz S, Purta E et al. (2009) MODOMICS: a database of RNA modification pathways. 2008 update. Nucleic Acids Research 37: D118–D121.

Dunin‐Horkawicz S, Czerwoniec A, Gajda MJ et al. (2006) MODOMICS: a database of RNA modification pathways. Nucleic Acids Research 34: D145–D149.

Dupasquier M, Kim S, Halkidis K, Gamper H and Hou YM (2008) tRNA integrity is a prerequisite for rapid CCA addition: implication for quality control. Journal of Molecular Biology 379: 579–588.

Englert M and Beier H (2005) Plant tRNA ligases are multifunctional enzymes that have diverged in sequence and substrate specificity from RNA ligases of other phylogenetic origins. Nucleic Acids Research 33: 388–399.

Fey J, Weil JH, Tomita K et al. (2002) Role of editing in plant mitochondrial transfer RNAs. Gene 286: 21–24.

Filipowicz W, Konarska M, Gross HJ and Shatkin AJ (1983) RNA 3′‐terminal phosphate cyclase activity and RNA ligation in HeLa cell extract. Nucleic Acids Research 11: 1405–1418.

Gerber AP and Keller W (1999) An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science 286: 1146–1149.

Gott JM and Emeson RB (2000) Functions and mechanisms of RNA editing. Annual Review of Genetics 34: 499–531.

Gott JM, Somerlot BH and Gray MW (2010) Two forms of RNA editing are required for tRNA maturation in Physarum mitochondria. RNA 16: 482–488.

Guerrier‐Takada C, Gardiner K, Marsh T, Pace N and Altman S (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35: 849–857.

Heinemann IU, Soll D and Randau L (2010) Transfer RNA processing in archaea: unusual pathways and enzymes. FEBS Letters 584: 303–309.

Holzmann J, Frank P, Loffler E et al. (2008) RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell 135: 462–474.

Houseley J and Tollervey D (2009) The many pathways of RNA degradation. Cell 136: 763–776.

Jackman JE and Phizicky EM (2006) tRNAHis guanylyltransferase adds G‐1 to the 5′ end of tRNAHis by recognition of the anticodon, one of several features unexpectedly shared with tRNA synthetases. RNA 12: 1007–1014.

Kadaba S, Krueger A, Trice T et al. (2004) Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes & Development 18: 1227–1240.

Kirsebom LA and Trobro S (2009) RNase P RNA‐mediated cleavage. IUBMB Life 61: 189–200.

Kotelawala L, Grayhack EJ and Phizicky EM (2008) Identification of yeast tRNA Um(44) 2′‐O‐methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNA(Ser) species. RNA 14: 158–169.

Lai LB, Vioque A, Kirsebom LA and Gopalan V (2010) Unexpected diversity of RNase P, an ancient tRNA processing enzyme: challenges and prospects. FEBS Letters 584: 287–296.

Laski FA, Fire AZ, RajBhandary UL and Sharp PA (1983) Characterization of tRNA precursor splicing in mammalian extracts. Journal of Biological Chemistry 258: 11974–11980.

Lavrov DV, Brown WM and Boore JL (2000) A novel type of RNA editing occurs in the mitochondrial tRNAs of the centipede Lithobius forficatus. Proceedings of the National Academy of Sciences of the USA 97: 13738–13742.

Leigh J and Lang BF (2004) Mitochondrial 3′ tRNA editing in the jakobid Seculamonas ecuadoriensis: a novel mechanism and implications for tRNA processing. RNA 10: 615–621.

Levinger L, Morl M and Florentz C (2004) Mitochondrial tRNA 3′ end metabolism and human disease. Nucleic Acids Research 32: 5430–5441.

Li H, Trotta CR and Abelson J (1998) Crystal structure and evolution of a transfer RNA splicing enzyme. Science 280: 279–284.

Lonergan KM and Gray MW (1993) Editing of transfer RNAs in Acanthamoeba castellanii mitochondria. Science 259: 812–816.

McCraith SM and Phizicky EM (1991) An enzyme from Saccharomyces cerevisiae uses NAD+ to transfer the splice junction 2′‐phosphate from ligated tRNA to an acceptor molecule. Journal of Biological Chemistry 266: 11986–11992.

Morl M and Marchfelder A (2001) The final cut. The importance of tRNA 3′‐processing. EMBO Reports 2: 17–20.

Nasr F and Filipowicz W (2000) Characterization of the Saccharomyces cerevisiae cyclic nucleotide phosphodiesterase involved in the metabolism of ADP‐ribose 1″,2″‐cyclic phosphate. Nucleic Acids Research 28: 1676–1683.

Phizicky EM and Alfonzo JD (2010) Do all modifications benefit all tRNAs? FEBS Letters 584: 265–271.

Phizicky EM, Schwartz RC and Abelson J (1986) Saccharomyces cerevisiae tRNA ligase. Purification of the protein and isolation of the structural gene. Journal of Biological Chemistry 261: 2978–2986.

Randau L, Schroder I and Soll D (2008) Life without RNase P. Nature 453: 120–123.

Randau L, Stanley BJ, Kohlway A et al. (2009) A cytidine deaminase edits C to U in transfer RNAs in Archaea. Science 324: 657–659.

Sawaya R, Schwer B and Shuman S (2003) Genetic and biochemical analysis of the functional domains of yeast tRNA ligase. Journal of Biological Chemistry 278: 43928–43938.

Schiffer S, Rosch S and Marchfelder A (2002) Assigning a function to a conserved group of proteins: the tRNA 3′‐processing enzymes. EMBO Journal 21: 2769–2777.

Schurer H, Schiffer S, Marchfelder A and Morl M (2001) This is the end: processing, editing and repair at the tRNA 3′‐terminus. Biological Chemistry 382: 1147–1156.

Shull NP, Spinelli SL and Phizicky EM (2005) A highly specific phosphatase that acts on ADP‐ribose 1′′‐phosphate, a metabolite of tRNA splicing in Saccharomyces cerevisiae. Nucleic Acids Research 33: 650–660.

Spinelli SL, Malik HS, Consaul SA and Phizicky EM (1998) A functional homolog of a yeast tRNA splicing enzyme is conserved in higher eukaryotes and in Escherichia coli. Proceedings of the National Academy of Sciences of the USA 95: 14136–14141.

Sprinzl M, Horn C, Brown M, Ioudovitch A and Steinberg S (1998) Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Research 26: 148–153.

Thompson DM and Parker R (2009) Stressing out over tRNA cleavage. Cell 138: 215–219.

Thompson M, Haeusler RA, Good PD and Engelke DR (2003) Nucleolar clustering of dispersed tRNA genes. Science 302: 1399–1401.

Trotta CR, Miao F, Arn EA et al. (1997) The yeast tRNA splicing endonuclease: a tetrameric enzyme with two active site subunits homologous to the archaeal tRNA endonucleases. Cell 89: 849–858.

Trotta CR, Paushkin SV, Patel M, Li H and Peltz SW (2006) Cleavage of pre‐tRNAs by the splicing endonuclease requires a composite active site. Nature 441: 375–377.

Waldron C and Lacroute F (1975) Effect of growth rate on the amounts of ribosomal and transfer ribonucleic acids in yeast. Journal of Bacteriology 122: 855–865.

Zhu L and Deutscher MP (1987) tRNA nucleotidyltransferase is not essential for E. coli viability. EMBO Journal 6: 2473–2477.

Zillman M, Gorovsky MA and Phizicky EM (1992) HeLa cells contain a 2′‐phosphate‐specific phosphotransferase similar to a yeast enzyme implicated in tRNA splicing. Journal of Biological Chemistry 267: 10289–10294.

Zillmann M, Gorovsky MA and Phizicky EM (1991) Conserved mechanism of tRNA splicing in eukaryotes. Molecular & Cellular Biology 11: 5410–5416.

Zofallova L, Guo Y and Gupta R (2000) Junction phosphate is derived from the precursor in the tRNA spliced by the archaeon Haloferax volcanii cell extract. RNA 6: 1019–1030.

Further Reading

Grosjean H (2009) DNA and RNA Modification Enzymes: Structure, Mechanism, Function and Evolution. Austin, TX: Landes Bioscience.

Grosjean H and Benne R (1998) Modification and Editing of RNA. Washington, DC: ASM Press.

Marck C and Grosjean H (2002) tRNomics: analysis of tRNA genes from 50 genomes of Eukarya, Archaea, and Bacteria reveals anticodon‐sparing strategies and domain‐specific features. RNA 8: 1189–1232.

Phizicky EM and Hopper AK (2010) tRNA biology charges to the front. Genes & Development 24: 1832–1860.

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

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Jackman, Jane E(Dec 2010) tRNA Biogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020894]