Transfer RNA Synthesis and Regulation

Yukimatsu Toh, AIST, Tsukuba, Japan
Hiroyuki Hori, Ehime University, Ehime, Japan
Kozo Tomita, AIST, Tsukuba, Japan
Takuya Ueda, University of Tokyo, Kashiwa, Japan
Kimitsuna Watanabe, AIST, Tokyo, Japan

Published online: December 2009

DOI: 10.1002/9780470015902.a0000529.pub2

Transfer ribonucleic acid (tRNA) is primarily synthesized from tRNA gene through transcription by RNA polymerase and becomes the mature form via several steps: processing, splicing, CCA addition and posttranscriptional modification. Primary transcripts of tRNA genes contain 5¢ and 3¢ extra sequences, which are removed by a set of responsible nucleases, and introns in some cases, which are spliced out by a specific endonuclease. The resultant two fragments are joined by RNA ligase. The CCA sequences present at 3¢-termini of all mature tRNAs are not encoded in tRNA genes in some species and posttranscriptionally added by a CCA-adding enzyme. All mature tRNA molecules contain modified nucleotides made by modification enzymes and which are considered to be involved in stabilization of tRNA structure, in decoding properties and in correct processing. The concentration of individual tRNA molecules is controlled to maintain cellular functions.

Key concepts:

  • tRNA is synthesized from tRNA gene by RNA polymerase and matured through processing, splicing, CCA addition and posttranscriptional modification.
  • Synthesis of tRNA is regulated by promoter activity and specific factors (ppGpp and/or pppGpp in prokaryotes and Maf1 in eukaryotes) depending on the nutrient condition of the cells.
  • The relative amounts of tRNA are regulated by several factors; the copy number of the tRNA gene, transcriptional activity aforementioned and tRNA degradation by a number of nucleases.
  • Primary transcripts of tRNA genes contain 5¢ and 3¢ extra sequences, which are removed by a set of responsible nucleases.
  • In some cases tRNA transcripts contain introns, which are spliced out by a specific endonuclease and the resultant two fragments are joined by RNA ligase.
  • CCA-adding enzyme regulates the amount of active tRNA by repairing CCA sequence at the C-terminal of tRNA.
  • tRNA possesses a variety of modified nucleotides which are introduced by modification enzymes during or after the processing, splicing and transport steps.
  • Several modifications in tRNA play important roles in the translation process, such as enhancement, expansion, restriction and/or alteration of codon–anticodon interactions, stabilization of tRNA structure, recognition by aminoacyl-tRNA synthetase, etc.

Keywords: promoter; tRNA modification; tRNA processing; tRNA intron; CCA-adding enzyme; transcriptional control

Figure 1. Relative codon usages and tRNA amounts in Micrococcus luteus. Codon usages and amounts of isoacceptor tRNAs are shown relative to the most abundant, which is taken as 100. ND, not detected; * indicates a modified nucleotide; Y refers to U or C and I is inosine. Reprinted with permission from Kano A, Andachi Y, Ohana T and Osawa S (1991) Novel anticodon composition of transfer RNAs in Micrococcus luteus, a bacterium with a high genomic G+C content. Correlation with codon usage. Journal of Molecular Biology 221: 387–401. Copyright © 1991 Academic Press.
Figure 2. Modified nucleotides frequently found in tRNAs.
Figure 3. Location of modified nucleosides in tRNA*. *Numbering of nucleotides conforms to that based on the secondary structure of yeast tRNAPhe; the solid and dotted lines show the secondary and tertiary base pairs, respectively.
close
 References
    Abe T, Ikemura T, Ohara Y et al. (2009) tRNADB-CE: tRNA gene database curated manually by experts. Nucleic Acids Research 37: D163–D168.
    Alexandrov A, Chernyakov I, Gu W et al. (2006) Rapid tRNA decay can result from lack of nonessential modifications. Molecular Cell 21: 87–96.
    Anderson J, Phan L, Cuesta R et al. (1998) The essential Gcd10p-Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA. Genes & Development 12: 3650–3652.
    Blattner FR, Plunkett G III, Bloch CA et al. (1997) The complete genome sequence of E. coli K-12. Science 277: 1453–1474.
    Calvin K and Li H (2008) RNA-splicing endonuclease structure and function. Cellular and Molecular Life Sciences 65: 1176–1185.
    Ciesla M and Boguta M (2008) Regulation of RNA polymerase III transcription by Maf1 protein. Acta Biochimica Polonica 55: 215–225.
    Ciesla M, Towpik J, Graczyk D et al. (2007) Maf1 is involved in coupling carbon metabolism to RNA polymerase III transcription. Molecular and Cellular Biology 27: 7693–7702.
    Deutscher MP (1990) Transfer RNA nucleotidyltransferase. Methods in Enzymology 181: 434–439.
    Droogmans L, Roovers M, Bujnicki JM et al. (2003) Cloning and characterization of tRNA (m1A58) methyltransferase (TrmI) from Thermus thermophilus HB27, a protein required for cell growth at extreme temperatures. Nucleic Acids Research 31: 2148–2156.
    Enqlert 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.
    Geiduschek EP and Tocchini-Valentine GP (1988) Transcription by RNA polymerase III. Annual Review of Biochemistry 57: 873–914.
    Hofmann A, Zdanov A, Genschik P et al. (2000) Structure and mechanism of activity of the cyclic phosphodiesterase of Appr>p, a product of the tRNA splicing reaction. EMBO Journal 19: 6207–6217.
    Holzmann J, Frank P, Löffler E et al. (2008) RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell 135: 462–474.
    Hur S and Stroud RM (2007) How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA. Molecualr Cell 26: 189–203.
    Ikemura T (1982) Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. Differences in synonymous codon choice patterns of yeast and E. coli with reference to the abundance of isoaccepting transfer RNAs. Journal of Molecular Biology 158: 573–597.
    Intine RV, Sakulich AL, Koduru SB et al. (2000) Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366. Molecular Cell 6: 329–348.
    Jühling F, Morl M, Hartmann RK et al. (2009) tRNAdb 2009: compilation of tRNA sequences and tRNA genes. Nucleic Acids Research 37: D159–D162.
    Kaneko T, Suzuki T, Kapushoc ST et al. (2003) Wobble modification differences and subcellular localization of tRNAs in Leishmania tarentolae: implication for tRNA sorting mechanism. EMBO Journal 22: 657–667.
    Kirino Y, Yasukawa T, Ohta S et al. (2004) Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease. Proceedings of the National Academy of Sciences of the USA 101: 15070–15075.
    Kirsebom LA (2007) RNase P RNA mediated cleavage: substrate recognition and catalysis. Biochimie 89: 1183–1194.
    Komine Y, Adachi T, Inokuchi H and Ozeki H (1990) Genomic organisation and physical mapping of the transfer RNA genes in E. coli K12. Journal of Molecular Biology 212: 579–598.
    Lauhon CT, Erwin WM and Ton GN (2004) Substrate specificity for 4thiouridine modification in E. coli. Journal of Biological Chemistry 279: 23022–23029.
    Li F, Xiong Y, Wang J et al. (2002) Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its complexes with ATP or CTP. Cell 111: 815–824.
    Li Z and Deutscher MP (1996) Maturation pathways for E. coli tRNA precursors: a random multienzyme process in vivo. Cell 86: 503–512.
    Lowe TM and Eddy SR (1997) tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Research 25: 955–964.
    Lund E and Dahlberg JE (1998) Proofreading and aminoacylation of tRNAs before export from nucleus. Science 282: 2003–2004.
    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.
    Miller DL and Martin NC (1983) Characterization of the yeast mitochondrial locus necessary for tRNA biosynthesis: DNA sequence analysis and identification of a new transcript. Cell 34: 911–917.
    Muto A, Andachi H, Yuzawa F, Yomao F and Osawa S (1990) The organization and evolution of transfer RNA genes in Mycoplasma capricolum. Nucleic Acids Research 18: 5037–5043.
    Noma A, Kirino Y, Ikeuchi Y and Suzuki T (2006) Biosynthesis of wybutosine, a hyper-modifued nucleoside in eukaryotic phenylalanine tRNA. EMBO Journal 25: 2142–2154.
    Okabe M, Tomita K, Ishitani R et al. (2003) Divergent evolution of trinucleotide polymerization revealed by an archaeal CCA-adding enzyme structure. EMBO Journal 22: 5918–5927.
    Perret V, Garcia A, Grosjean H et al. (1990) Relaxation of a transfer RNA specificity by removal of modified nucleotides. Nature 344: 787–789.
    Phizicky EM, Schwartz RC and Abelson J (1986) Saccharomyces cerevisiae tRNA ligase. Purification of the protein and isolation of the structure gene. Journal of Biological Chemistry 261: 2978–2986.
    Randau L, Schroder I and Söll D (2008) Life without RNase P. Nature 453: 120–123.
    Schwer B, Aronova A, Ramirez A, Braun P and Shuman S (2008) Mammalian 2¢, 3¢ cyclic nucleotide phsophodiesterase (CNP) can function as a tRNA splicing enzyme in vivo. RNA 14: 204–210.
    Shigi N, Sakaguchi Y, Asai S, Suzuki T and Watanabe K (2008) Common thiolation mechanism in the biosynthesis of tRNA thiouridine and sulphur-containing cofactors. EMBO Journal 27: 3267–3278.
    Soma A, Onodera A, Sugahara J et al. (2007) Permuted tRNA genes expressed via a circular RNA intermediate in Cyanidioschyzon merolae. Science 318: 450–453.
    Späth B, Canino G and Marchfelder A (2007) tRNAase Z: the end is not sight. Cellular and Molecular Life Sciences 64: 2404–2412.
    Suzuki T, Suzuki T, Wada T, Saigo K and Watanabe K (2002) Taurine as a constituent of mitochondrial tRNA: new insights into the functions of taurine and human mitochondrial diseases. EMBO Journal 21: 6581–6589.
    Tomita K, Fukai S, Ishitani R et al. (2004) Structural basis for template-independent RNA polymerization. Nature 430: 700–704.
    Tomita K, Ishitani R, Fukai S and Nureki O (2006) Complete crystallographic analysis of the dynamics of CCA sequence addition. Nature 443: 956–960.
    Tomita K and Weiner AM (2002) Closely related C- and A-adding enzymes collaborate to construct and repair the 3¢-terminal CCA of tRNA in Synechocystis sp. and Deinococcus radiodurans. Journal of Biological Chemistry 277: 48192–48198.
    Tomita K and Weiner AM (2001) Collaboration between CC- and A-adding enzymes to built and repair the 3¢-terminal CCA in Aquifex aeolicus. Science 294: 1334–1336.
    Urbonavicius J, Durand JM and Björk GR (2002) Three modifications in the D and T arms of tRNA influence translation in E. coli and expression of virulence genes in Shigella flexneri. Journal of Bacteriology 184: 5348–5357.
    Walker SC and Engelke DR (2008) A protein-only RNase P in human mitochondria. Cell 135: 412–413.
    Wang LK and Shuman S (2005) Structure-function analysis of yeast tRNA ligase. RNA 11: 966–975.
    Watanabe K, Shinma M, Oshima T and Nishimura S (1976) Heat-induced stability of tRNA from an extreme thermophile, Thermus thermophilus. Biochemical and Biophysical Research Communications 72: 1137–1144.
    Xiong Y, Li F, Wang J, Weiner AM and Steitz TA (2003) Crystal structure of an Archaeal Class I CCA-Adding enzyme and its nucleotide complexes. Molecular Cell 12: 1165–1172.
    Xiong Y and Steitz TA (2004) Mechanism of transfer RNA maturation by CCA-adding enzyme without using an oligonucleotide template. Nature 430: 640–645.
    Yoo CJ and Wolin SL (1997) The yeast La protein is required for the 3¢ endonucleolytic cleavage that matures tRNA precursors. Cell 89: 393–402.
    Yue D, Maizels N and Weiner AM (1996) CCA-adding enzymes and poly(A) polymerase are all members of the same nucleotidyltransferase superfamily: characterization of the CCA-adding enzyme from the archaeal hyperthermophile Sulfolobus shibatae. RNA 2: 895–908.
 Further Reading
    book Söll D and RajBhandary U (eds) (1995) tRNA: Structure, Biosynthesis and Function. Washington, DC: American Society for Microbiology.

Related Sub-Topics:

Transcription of DNA | Transcriptional Regulation | RNA Structure and Function | Noncoding RNA | Posttranscriptional Modification | Biomolecular Interactions | Nucleic Acids: Structure, Function, Metabolism
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Transfer RNA Synthesis and Regulation
 
How to Cite close
Toh, Yukimatsu, Hori, Hiroyuki, Tomita, Kozo, Ueda, Takuya, and Watanabe, Kimitsuna(Dec 2009) Transfer RNA Synthesis and Regulation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000529.pub2]