Transfer RNA Synthesis and Regulation

Abstract

Transfer ribonucleic acid (tRNA), which is primarily transcribed from tRNA genes by RNA polymerase, matures via several steps: processing, splicing, CCA addition and post‐transcriptional modifications. Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases. In addition, some primary transcripts contain introns, which are spliced out by specific endonucleases or in self‐splicing reactions. The ligation of exons generally requires a tRNA ligase. In some species, the CCA sequences present at the 3′‐termini of all mature tRNAs are not encoded in the tRNA genes, but are added post‐transcriptionally by a CCA‐adding enzyme. All mature tRNA molecules contain modified nucleotides, generated by specific tRNA modification enzymes or guide RNA systems. These modified nucleotides are involved in stabilisation of tRNA structure, decoding, tRNA quality control, regulation of subcellular localisation of tRNAs and immune responses against infectious organisms.

Key Concepts:

  • tRNA is transcribed from tRNA genes by RNA polymerase, and matures through processing, splicing, CCA addition and post‐transcriptional 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 conditions of the cell.

  • The relative amounts of tRNA are regulated by several factors: copy number of tRNA genes, transcriptional activity, and degradation by various nucleases.

  • Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases.

  • In some cases, tRNA transcripts contain introns, which are spliced out by specific endonuclease or the group I intron reaction. The two resultant fragments are joined by RNA ligase or the self‐splicing reaction.

  • CCA‐adding enzyme regulates the amount of active tRNA by introducing the CCA sequence at the C‐terminus of tRNA.

  • tRNA possesses a variety of modified nucleotides, which are introduced by specific tRNA modification enzymes.

  • Several modifications of tRNA play important roles in the translation process: promotion, expansion, restriction, and/or alteration of codon–anticodon interactions; stabilisation of tRNA structure; recognition by translation factors and aminoacyl‐tRNA synthetases; etc.

  • Several modified nucleotides in tRNA are involved in RNA quality control systems, regulation of tRNA transport, infection and immune responses.

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

Figure 1.

Relative codon usages and tRNA levels in Micrococcus luteus. Codon usages and amounts of isoacceptor tRNAs are shown relative to the most abundant species (defined 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 et al. () © Elsevier.

Figure 2.

Modified nucleotides frequently found in tRNAs.

Figure 3.

Location of modified nucleosides in tRNA*. *Numbering of nucleotides confirms to 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.

Alexandrov A, Martzen MR and Phizicky EM (2002) Two proteins that form a complex are required for 7‐methylguanosine modification of yeast tRNA. RNA 8: 1253–1266.

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.

Anderson J, Phan L and Hinnebusch AG (2000) The Gcd10p/Gcd14p complex is the essential two‐subunit tRNA(1‐methyladenosine) methyltransferase of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the USA 97: 5173–5178.

Armengaud J, Urbonavicius J, Fernandez B et al. (2004) N2‐methylation of guanosine at position 10 in tRNA is catalyzed by a THUMP domain‐containing, S‐adenosylmethionine‐dependent methyltransferase, conserved in Archaea and Eukaryota. Journal of Biological Chemistry 279: 37142–37152.

Aström SU and Byström AS (1994) Rit1, a tRNA backbone‐modifying enzyme that mediates initiator and elongator tRNA discrimination. Cell 79: 535–546.

Auxilien S, El Khadali F, Rasmussen A, Douthwaite S and Grosjean H (2007) Archease from Pyrococcus abyssi improves substrate specificity and solubility of a tRNA m5C methyltransferase. Journal of Biological Chemistry 282: 18711–18721.

Awai T, Kimura S, Tomikawa C et al. (2009) Aquifex aeolicus tRNA (N2,N2‐guanine)‐dimethyltransferase (Trm1) catalyzes transfer of methyl groups not only to guanine 26 but also to guanine 27 in tRNA. Journal of Biological Chemistry 284: 20467–20478.

Awai T, Ochi A, Ihsanawati et al. (2011) Substrate tRNA recognition mechanism of a multisite‐specific tRNA methyltransferase, Aquifex aeolicus Trm1, based on the X‐ray crystal structure. Journal of Biological Chemistry 286: 35236–35246.

Becker HF, Motorin Y, Planta RJ and Grosjean H (1997) The yeast gene YNL292w encodes a pseudouridine synthase (Pus4) catalyzing the formation of psi55 in both mitochondrial and cytoplasmic tRNAs. Nucleic Acids Research 25: 4493–4499.

Begley U, Dyavaiah M, Patil A et al. (2007) Trm9‐catalyzed tRNA modifications link translation to the DNA damage response. Molecular Cell 28: 860–870.

Behm‐Ansmant I, Grosjean H, Massenet S, Motorin Y and Branlant C (2004) Pseudouridylation at position 32 of mitochondrial and cytoplasmic tRNAs requires two distinct enzymes in Saccharomyces cerevisiae. Journal of Biological Chemistry 279: 52998–53006.

Benítez‐Páez A, Villarroya M, Douthwaite S, Gabaldón T and Armengod ME (2010) YibK is the 2′‐O‐methyltransferase TrmL that modifies the wobble nucleotide in Escherichia coli tRNA(Leu) isoacceptors. RNA 16: 2131–2143.

Bishop AC, Xu J, Johnson RC, Schimmel P and de Crécy‐Lagard V (2002) Identification of the tRNA‐dihydrouridine synthase family. Journal of Biological Chemistry 277: 25090–25095.

Björk GR, Jacobsson K, Nilsson K et al. (2001) A primordial tRNA modification required for the evolution of life? EMBO Journal 20: 231–239.

Björk GR, Wikström PM and Byström AS (1989) Prevention of translational frameshifting by the modified nucleoside 1‐methylguanosine. Science 244: 986–989.

Blattner FR, Plunkett G III, Bloch CA, Perna NT and Burland V (1997) The complete genome sequence of E. coli K‐12. Science 277: 1453–1474.

Bortolin ML, Bachellerie JP and Clouet‐d'Orval B (2003) In vitro RNP assembly and methylation guide activity of an unusual box C/D RNA, cis‐acting archaeal. Nucleic Acids Research 31: 6524–6535.

Brulé H, Elliott M, Redlak M, Zehner ZE and Holmes WM (2004) Isolation and characterization of the human tRNA‐(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein. Biochemistry 43: 9243–9255.

Brzezicha B, Schmidt M, Makalowska I et al. (2006) Identification of human tRNA:m5C methyltransferase catalysing intron‐dependent m5C formation in the first position of the anticodon of the pre‐tRNA Leu (CAA). Nucleic Acids Research 34: 6034–6043.

Caillet J and Droogmans L (1988) Molecular cloning of the Escherichia coli miaA gene involved in the formation of delta 2‐isopentenyl adenosine in tRNA. Journal of Bacteriology 170:4147–4152.

Calvin K and Li H (2008) RNA‐splicing endonuclease structure and function. Cellular and Molecular Life Sciences 65: 1176–1185.

Cavaillé J, Chetouani F and Bachellerie JP (1999) The yeast Saccharomyces cerevisiae YDL112w ORF encodes the putative 2′‐O‐ribose methyltransferase catalyzing the formation of Gm18 in tRNAs. RNA 5: 66–81.

Chen C, Huang B, Anderson JT et al. (2011) Unexpected accumulation of ncm(5)U and ncm(5)S(2) (U) in a trm9 mutant suggests an additional step in the synthesis of mcm(5)U and mcm(5)S(2)U. PLoS One 6: e20783.

Chernyakov I, Whipple JM, Kotelawala L et al. (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.

Christian T, Evilia C, Williams S and Hou YM (2004) Distinct origins of tRNA(m1G37) methyltransferase. Journal of Molecular Biology 339: 707–719.

Chujo T and Suzuki T (2012) Trmt61B is a methyltransferase responsible for 1‐methyladenosine at position 58 of human mitochondrial tRNAs. RNA 18: 2269–2276.

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.

Clouet d'Orval B, Bortolin ML, Gaspin C and Bachellerie JP (2001) Box C/D RNA guides for the ribose methylation of archaeal tRNAs. The tRNATrp intron guides the formation of two ribose‐methylated nucleosides in the mature tRNATrp. Nucleic Acids Research 29: 4518–4529.

Constantinesco F, Benachenhou N, Motorin Y and Grosjean H (1998) The tRNA(guanine‐26,N2‐N2) methyltransferase (Trm1) from the hyperthermophilic archaeon Pyrococcus furiosus: cloning, sequencing of the gene and its expression in Escherichia coli. Nucleic Acids Research 26: 3753–3761.

Cortese R, Kammen HO, Spengler SJ and Ames BN (1974) Biosynthesis of pseudouridine in transfer ribonucleic acid. Journal of Biological Chemistry 249: 1103–1108.

De Bie LG, Roovers M, Oudjama Y et al. (2003) The yggH gene of Escherichia coli encodes a tRNA (m7G46) methyltransferase. Journal of Bacteriology 185: 3238–3243.

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.

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.

Englert M, Sheppard K, Aslanian A, Yates JR 3rd and Söll D (2011) Archaeal 3′‐phosphate RNA splicing ligase characterization identifies the missing component in tRNA maturation. Proceedings of the Sciences of the USA 108: 1290–1295.

Englert M, Sheppard K, Gundllapalli S, Beier H and Söll D (2010) Branchiostoma floridae has separate healing and sealing enzymes for 5′‐phosphate RNA ligation. Proceedings of the National Academy of Sciences of the USA 107: 16834–16839.

Farabaugh PJ and Bjork GR (1999) How translational accuracy influences reading frame maintenance. EMBO Journal 18: 1427–1434.

Filipowicz W and Shatkin AJ (1983) Origin of splice junction phosphate in tRNAs processed by HeLa cell extract. Cell 32: 547–557.

Fislage M, Roovers M, Tuszynska I et al. (2012) Crystal structures of the tRNA:m2G6 methyltransferase Trm14/TrmN from two domains of life. Nucleic Acids Research 40: 5149–5161.

Fujishima K, Sugahara J, Miller CS et al. (2011) A novel three‐unit tRNA splicing endonuclease found in ultrasmall Archaea possesses broad substrate specificity. Nucleic Acids Research 39: 9695–9704.

Gehrig S, Eberle ME, Botschen F et al. (2012) Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. Journal of Experimental Medicine 209: 225–233.

Geiduschek EP and Tocchini‐Valentine GP (1988) Transcription by RNA polymerase III. Annual Review of Biochemistry 57: 873–914.

Goto‐Ito S, Ito T, Kuratani M, Bessho Y and Yokoyama S (2009) Tertiary structure checkpoint at anticodon loop modification in tRNA functional maturation. Nature Structural & Molecular Biology 16: 1109–1115.

Gu X, Ivanetic KM and Santi DV (1996) Recognition of the T‐arm of tRNA by tRNA (m5U54)‐methyltransferase is not sequence specific. Biochemistry 35: 11652–11659.

Guelorget A, Roovers M, Guérineau V et al. (2010) Insights into the hyperthermostability and unusual region‐specificity of archaeal Pyrococcus abyssi tRNA m1A57/58 methyltransferase. Nucleic Acids Research 38: 6206–6218.

Gurha P and Gupta R (2008) Archaeal Pus10 proteins can produce both pseudouridine 54 and 55 in tRNA. RNA 14: 2521–2527.

Guy MP, Podyma BM and Preston MA (2012) Yeast Trm7 interacts with distinct proteins for critical modifications of the tRNAPhe anticodon loop. RNA 18: 1921–1933.

Hamdane D, Argentini M, Cornu D, Golinelli‐Pimpaneau B and Fontecave M (2012) FAD/folate‐dependent tRNA methyltransferase: flavin as a new methyl‐transfer agent. Journal of the American Chemical Society 134: 19739–19745.

Hirata A, Fujishima K, Yamagami R et al. (2012) X‐ray structure of the fourth type of archaeal tRNA splicing endonuclease: insights into the evolution of a novel three‐unit composition and a unique loop involved in broad substrate specificity. Nucleic Acids Research 40: 10554–10566.

Hirata A, Kitajima T and Hori H (2011) Cleavage of intron from the standard or non‐standard position of the precursor tRNA by the splicing endonuclease of Aeropyrum pernix, a hyper‐thermophilic Crenarchaeon, involves a novel RNA recognition site in the Crenarchaea specific loop. Nucleic Acids Research 39: 9376–9389.

Hoang C and Ferre‐D'Amare AR (2001) Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA‐modifying enzyme. Cell 107: 929–939.

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.

Hopper AK, Furukawa AH, Pham HD and Martin NC (1982) Defects in modification of cytoplasmic and mitochondrial transfer RNAs are caused by single nuclear mutations. Cell 28: 543–550.

Hori H, Yamazaki N, Matsumoto T et al. (1998) Substrate recognition of tRNA (Guanosine‐2′‐)‐methyltransferase from Thermus thermophilus HB27. Journal of Biological Chemistry 273: 25721–25727.

Hur S and Stroud RM (2007) How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA. Molecular Cell 26: 189–203.

Ihsanawati B, Nishimoto M, Higashijima K et al. (2008) Crystal structure of tRNA N2,N2‐guanosine dimethyltransferase Trm1 from Pyrococcus horikoshii. Journal of Molecular Biology 383: 871–884.

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.

Ikeuchi Y, Kimura S, Numata T et al. (2010) Agmatine‐conjugated cytidine in a tRNA anticodon is essential for AUA decoding in archaea. Nature Chemical Biology 6: 277–282.

Ikeuchi Y, Shigi N, Kato J, Nishimura A and Suzuki T (2006) Mechanistic insights into sulfur relay by multiple sulfur mediators involved in thiouridine biosynthesis at tRNA wobble positions. Molecular Cell 21: 97–108.

Ikeuchi Y, Soma A, Ote T et al. (2005) Molecular mechanism of lysidine synthesis that determines tRNA identity and codon recognition. Molecular Cell 19: 235–246.

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..

Ishida K, Kunibayashi T, Tomikawa C et al. (2011) Pseudouridine at position 55 in tRNA controls the contents of other modified nucleotides for low‐temperature adaptation in the extreme‐thermophilic eubacterium Thermus thermophilus. Nucleic Acids Research 39: 2304–2318.

Ishitani R, Nureki O, Nameki N et al. (2003) Alternative tertiary structure of tRNA for recognition by a posttranscriptional modification enzyme. Cell 113: 383–394.

Joardar A, Malliahgari SR, Skariah G and Gupta R (2011) 2′‐O‐methylation of the wobble residue of elongator pre‐tRNA(Met) in Haloferax volcanii is guided by a box C/D RNA containing unique features. RNA Biology 8: 782–791.

Jöckel S, Nees G, Sommer R et al. (2012) The 2′‐O‐methylation status of a single guanosine controls transfer RNA‐mediated Toll‐like receptor 7 activation or inhibition. Journal of Experimental Medicine 209: 235–241.

Jühling F, Morl M, Hartmann RK et al. (2009) tRNAdb 2009: compilation of tRNA sequences and tRNA genes. Nucleic Acids Research 37: D159–D162.

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.

Kammen HO, Marvel CC, Hardy L and Penhoet EE (1988) Purification, structure, and properties of Escherichia coli tRNA pseudouridine synthase I. Journal of Biological Chemistry 263: 2255–2263.

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.

Kano A, Andachi Y, Ohama 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.

Kawai G, Yamamoto Y, Kamimura T et al. (1992) Conformational rigidity of specific pyrimidine residues in tRNA arises from posttranscriptional modifications that enhance steric interaction between the base and the 2′‐hydroxyl group. Biochemistry 31: 1040–1046.

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.

Kuratani M, Hirano M, Goto‐Ito S et al. (2010) Crystal structure of Methanocaldococcus jannaschii Trm4 complexed with sinefungin. Journal of Molecular Biology 401: 323–333.

Lauhon CT, Erwin WM and Ton GN (2004) Substrate specificity for 4‐thiouridine modification in Escherichia coli. Journal of Biological Chemistry 279: 23022–23029.

Lee SR and Collins K (2005) Starvation‐induced cleavage of the tRNA anticodon loop in Tetrahymena thermophila. Journal of Biological Chemistry 280: 42744–42749.

Leulliot N, Chaillet M, Durand D et al. (2008) Structure of the yeast tRNA m7G methylation complex. Structure 16: 52–61.

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

Li Z and Deutscher MP (1996) Maturation pathways for E. coli tRNA precursors: a random multienzyme process in vivo. Cell 86: 503–512.

Liu RJ, Zhou M, Fang ZP et al. (2013) The tRNA recognition mechanism of the minimalist SPOUT methyltransferase, TrmL. Nucleic Acids Research 41: 7828–7842.

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.

Mandal D, Köhrer C, Su D et al. (2010) Agmatidine, a modified cytidine in the anticodon of archaeal tRNA(Ile), base pairs with adenosine but not with guanosine. Proceedings of the National Academy of Sciences of the USA 107: 2872–2877.

Marck C and Grosjean H (2003) Identification of BHB splicing motifs in intron‐containing tRNAs from 18 archaea: evolutionary implications. RNA 9: 1516–1531.

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.

Menezes S, Gaston KW, Krivos KL et al. (2011) Formation of m2G6 in Methanocaldococcus jannaschii tRNA catalyzed by the novel methyltransferase Trm14. Nucleic Acids Research 39: 7641–7655.

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.

Mitchell M, Xue S, Erdman R et al. (2009) Crystal structure and assembly of the functional Nanoarchaeum equitans tRNA splicing endonuclease. Nucleic Acids Research 37: 5793–5802.

Miyauchi K, Kimura S and Suzuki T (2013) A cyclic form of N6‐threonylcarbamoyladenosine as a widely distributed tRNA hypermodification. Nature Chemical Biology 9: 105–111.

Moukadiri I, Garzón MJ, Björk GR and Armengod ME (2014) The output of the tRNA modification pathways controlled by the Escherichia coli MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species. Nucleic Acids Research 42: 2602–2623.

Muller S, Fourmann JB, Loegler C, Charpentier B and Branlant C (2007) Identification of determinants in the protein partners aCBF5 and aNOP10 necessary for the tRNA:Psi55‐synthase and RNA‐guided RNA:Psi‐synthase activities. Nucleic Acids Research 35: 5610–5624.

Muramatsu T, Nishikawa K, Nemoto F et al. (1988) Codon and amino‐acid specificities of a transfer RNA are both converted by a single post‐transcriptional modification. Nature 336: 179–181.

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.

Nishimasu H, Ishitani R, Yamashita K et al. (2009) Atomic structure of a folate/FAD‐dependent tRNA T54 methyltransferase. Proceedings of the National Academy of Sciences of the USA 106: 8180–8185.

Noma A, Kirino Y, Ikeuchi Y and Suzuki T (2006) Biosynthesis of wybutosine, a hyper‐modified nucleoside in eukaryotic phenylalanine tRNA. EMBO Journal 25: 2142–2154.

Nurse K, Wrzesinski J, Bakin A, Lane BG and Ofengand J (1995) Purification, cloning, and properties of the tRNA psi 55 synthase from Escherichia coli. RNA 1: 102–112.

Ochi A, Makabe K, Yamagami R et al. (2013) The catalytic domain of topological knot tRNA methyltransferase (TrmH) discriminates between substrate tRNA and nonsubstrate tRNA via an induced‐fit process. Journal of Biological Chemistry 288: 25562–25574.

Ohira T and Suzuki T (2011) Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast. Proceedings of the National Academy of Sciences of the USA 108: 10502–10507.

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.

Okada N, Noguchi S, Kasai H et al. (1979) Novel mechanism of post‐transcriptional modification of tRNA. Insertion of bases of Q precursors into tRNA by a specific tRNA transglycosylase reaction. Journal of Biological Chemistry 254: 3067–3073.

Okamoto H, Watanabe K, Ikeuchi Y et al. (2004) Substrate tRNA recognition mechanism of tRNA (m7G46) methyltransferase from Aquifex aeolicus. Journal of Biological Chemistry 279: 49151–49159.

Osawa T, Kimura S, Terasaka N, Numata T and Suzuki T (2011) Structural basis of tRNA agmatinylation essential for AUA codon decoding. Nature Structural & Molecular Biology 18: 1275–1280.

Pan H, Agarwalla S, Moustakas DT, Finer‐Moore J and Stroud RM (2003) Structure of tRNA pseudouridine synthase TruB and its RNA complex: RNA recognition through a combination of rigid docking and induced fit. Proceedings of the National Academy of Sciences of the USA 100: 12648–12653.

Paris Z, Horáková E, Rubio MA et al. (2013) The T. brucei TRM5 methyltransferase plays an essential role in mitochondrial protein synthesis and function. RNA 19: 649–658.

Perret V, Garcia A, Grosjean H et al. (1990) Relaxation of a transfer RNA specificity by removal of modified nucleotides. Nature 344: 787–789.

Persson BC, Jager G and Gustafsson C (1997) The spoU gene of Escherichia coli, the fourth gene of the spoT operon, is essential for tRNA (Gm18) 2′‐O‐methyltransferase activity. Nucleic Acids Research 25: 4093–4097.

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.

Pintard L, Lecointe F, Bujnicki JM et al. (2002) Trm7p catalyses the formation of two 2′‐O‐methylriboses in yeast tRNA anticodon loop. EMBO Journal 21: 1811–1820.

Popow J, Englert M, Weitzer S et al. (2011) HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science 331: 760–764.

Purta E, van Vliet F, Tkaczuk KL et al. (2006) The yfhQ gene of Escherichia coli encodes a tRNA:Cm32/Um32 methyltransferase. BMC Molecular Biology 7: 23.

Randau L, Calvin K, Hall M et al. (2005) The heteromeric Nanoarchaeum equitans splicing endonuclease cleaves noncanonical bulge‐helix‐bulge motifs of joined tRNA halves. Proceedings of the National Academy of Sciences of the USA 102: 17934–17939.

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

Reinhold‐Hurek B and Shub DA (1992) Self‐splicing introns in tRNA genes of widely divergent bacteria. Nature 357: 173–176.

Roovers M, Hale C, Tricot C et al. (2006) Formation of the conserved pseudouridine at position 55 in archaeal tRNA. Nucleic Acids Research 34: 4293–4301.

Roovers M, Oudjama Y, Fislage M et al. (2012) The open reading frame TTC1157 of Thermus thermophilus HB27 encodes the methyltransferase forming N²‐methylguanosine at position 6 in tRNA. RNA 18: 815–824.

Roovers M, Wouters J, Bujnicki JM et al. (2004) A primordial RNA modification enzyme: the case of tRNA (m1A) methyltransferase. Nucleic Acids Research 32: 465–476.

Schwer B, Aronova A, Ramirez A, Braun P and Shuman S (2008) Mammalian 2′,3′ cyclic nucleotide phosphodiesterase (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.

Shigi N, Sakaguchi Y, Suzuki T and Watanabe K (2006) Identification of two tRNA thiolation genes required for cell growth at extremely high temperatures. Journal of Biological Chemistry 281: 14296–14306.

Singh SK, Gurha P, Tran EJ, Maxwell ES and Gupta R (2004) Sequential 2′‐O‐methylation of archaeal pre‐tRNATrp nucleotides is guided by the intron‐encoded but trans‐acting box C/D ribonucleoprotein of pre‐tRNA. Journal of Biological Chemistry 279: 47661–47671.

Soma A, Ikeuchi Y, Kanemasa S et al. (2003) An RNA‐modifying enzyme that governs both the codon and amino acid specificities of isoleucine tRNA. Molecular Cell 12: 689–698.

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 in sight. Cellular and Molecular Life Sciences 64: 2404–2412.

Suzuki T, Suzuki T, Wada K, Saigo T and Watanabe K (2002) Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO Journal 21: 6581–6589.

Takai K and Yokoyama S (2003) Roles of 5‐substituents of tRNA wobble uridines in the recognition of purine‐ending codons. Nucleic Acids Research 31: 6383–6391.

Takano A, Endo T and Yoshihisa T (2005) tRNA actively shuttles between the nucleus and cytosol in yeast. Science 309: 140–142.

Takemoto C, Spremulli LL, Benkowski LA et al. (2008) Unconventional decoding of the AUA codon as methionine by mitochondrial tRNAMet with the anticodon f5CAU as revealed with a mitochondrial in vitro translation system. Nucleic Acids Research 37: 1616–1627.

Tanaka N and Shuman S (2011) RtcB is the RNA ligase component of an Escherichia coli RNA repair operon. Journal of Biological Chemistry 286: 7727–7731.

Terasaka N, Kimura S, Osawa T, Numata T and Suzuki T (2011) Biogenesis of 2‐agmatinylcytidine catalyzed by the dual protein and RNA kinase TiaS. Nature Structural & Molecular Biology 18: 1268–1274.

Thompson DM, Lu C, Green PJ et al. (2008) tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA 14: 2095–2103.

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

Tocchini‐Valentini GD, Fruscoloni P and Tocchini‐Valentini GP (2005) Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea. Proceedings of the National Academy of Sciences of the USA 102: 15418–15422.

Tomikawa C, Ochi A and Hori H (2008) The C‐terminal region of thermophilic tRNA (m7G46) methyltransferase (TrmB) stabilizes the dimer structure and enhances fidelity of methylation. Proteins 71: 1400–1408.

Tomikawa C, Ohira T, Inoue Y et al. (2013) Distinct tRNA modifications in the thermo‐acidophilic archaeon, Thermoplasma acidophilum. FEBS Letters 587: 3575–3580.

Tomikawa C, Yokogawa T, Kanai T and Hori H (2010) N7‐methylguanine at position 46 (m7G46) in tRNA from Thermus thermophilus is required for cell viability through a tRNA modification network. Nucleic Acids Research 38: 942–957.

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 (2001) Collaboration between CC‐ and A‐adding enzymes to built and repair the 3′‐terminal CCA in Aquifex aeolicus. Science 294: 1334–1336.

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.

Trotta CR, Miao F, Arm 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.

Urbonavicius J, Armengaud J and Grosjean H (2006) Identity elements required for enzymatic formation of N2,N2‐dimethylguanosine from N2‐monomethylated derivative and its possible role in avoiding alternative conformations in archaeal tRNA. Journal of Molecular Biology 357: 387–399.

Urbonavicius J, Durand JM and Björk GR (2002) Three modifications in the D and T arms of tRNA influence translation in Escherichia coli and expression of virulence genes in Shigella flexneri. Journal of Bacteriology 184: 5348–5357.

Urbonavicius J, Qian Q, Durand JM, Hagervall TG and Björk GR (2001) Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO Journal 20: 4863–4873.

Urbonavicius J, Skouloubris S, Myllykallio H and Grosjean H (2005) Identification of a novel gene encoding a flavin‐dependent tRNA:m5U methyltransferase in bacteria‐‐evolutionary implications. Nucleic Acids Research 33: 3955–3964.

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.

Warner GJ, Berry MJ, Moustafa ME et al. (2000) Inhibition of selenoprotein synthesis by selenocysteine tRNA[Ser]Sec lacking isopentenyladenosine. Journal of Biological Chemistry 275: 28110–28119.

Watanabe K, Miyagawa R, Tomikawa C et al. (2013) Degradation of initiator tRNAMet by Xrn1/2 via its accumulation in the nucleus of heat‐treated HeLa cells. Nucleic Acids Research 41: 4671–4685.

Watanabe M, Nameki N, Matsuo‐Takasaki M, Nishimura S and Okada N (2001) tRNA recognition of tRNA‐guanine transglycosylase from a hyperthermophilic archaeon, Pyrococcus horikoshii. Journal of Biological Chemistry 276: 2387–2394.

Watanabe K, Oshima T, Saneyoshi M and Nishimura S (1974) Replacement of ribothymidine by 5‐methyl‐2‐thiouridine in sequence GT psi C in tRNA of an extreme thermophile. FEBS Letters 43: 59–63.

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.

Weixlbaumer A, Murphy FV 4th, Dziergowska A et al. (2007) Mechanism for expanding the decoding capacity of transfer RNAs by modification of uridines. Nature Structural & Molecular Biology 14: 498–502.

Wolf J, Gerber AP and Keller W (2002) tadA, an essential tRNA‐specific adenosine deaminase from Escherichia coli. EMBO Journal 21: 3841–3851.

Xing F, Martzen MR and Phizicky EM (2002) A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine modification of tRNA. RNA 8: 370–381.

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.

Xue S, Calvin K and Li H (2006) RNA recognition and cleavage by a splicing endonuclease. Science 312: 906–910.

Yamagami R, Yamashita K, Nishimasu H et al. (2012) The tRNA recognition mechanism of folate/FAD‐dependent tRNA methyltransferase (TrmFO). Journal of Biological Chemistry 287: 42480–42494.

Yarian C, Townsend H, Czestkowski W et al. (2002) Accurate translation of the genetic code depends on tRNA modified nucleosides. Journal of Biological Chemistry 277: 16391–16395.

Yasukawa T, Suzuki T, Ishii N, Ohta S and Watanabe K (2001) Wobble modification defect in tRNA disturbs codon‐anticodon interaction in a mitochondrial disease. EMBO Journal 20: 4794–4802.

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.

Yoshinari S, Shiba T, Inaoka DK et al. (2009) Functional importance of crenarchaea‐specific extra‐loop revealed by an X‐ray structure of a heterotetrameric crenarchaeal splicing endonuclease. Nucleic Acids Research 37: 4787–4798.

Yu F, Tanaka Y, Yamashita K et al. (2011) Molecular basis of dihydrouridine formation on tRNA. Proceedings of the National Academy of Sciences of the USA 108: 19593–19598.

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

Söll D and RajBhandary U (eds) (1995) tRNA: Structure, Biosynthesis and Function. Washington, DC: American Society for Microbiology.

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

* Required Field

How to Cite close
Hori, Hiroyuki, Tomikawa, Chie, Hirata, Akira, Toh, Yukimatsu, Tomita, Kozo, Ueda, Takuya, and Watanabe, Kimitsuna(Sep 2014) Transfer RNA Synthesis and Regulation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000529.pub3]