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MetaCyc Pathway: tRNA splicing
Inferred from experiment

Pathway diagram: tRNA splicing

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisNucleic Acid Processing

Some taxa known to possess this pathway include : Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Eukaryota

tRNAs are the molecular adapters that carry amino acids and enable the synthesis of proteins based on mRNAs transcribed from protein-coding genes. The active form of tRNA is generated by a combination of nuclease-based processing, the modification of select nucleosides, and finally charging with an amino acid via the tRNA charging.

The processing of tRNA in Archaea and Eukaryota involves the splicing of introns by a mechanism that involves three protein enzymes (unlike mRNA splicing, which is RNA catalyzed). While there are some examples of tRNA intron splicing in prokaryotes, that process occurs via the so called "primitive" autocatalytic mechanism and does not involve dedicated enzymes.

Much of the knowledge about tRNA intron splicing comes from the yeast Saccharomyces cerevisiae. The S. cerevisiae genome contains 272 tRNA genes of which 59, encoding ten different tRNAs, contain introns. These introns are 14-60 bases in length, and all interrupt the anticodon loop immediately 3' to the anticodon [Ogden84]. It has been estimated that ~500 000 molecules of tRNA are spliced per generation in yeast [Shull05].

Splicing of the introns from the precursor tRNA is accomplished through the action of a site-specific tRNA-splicing endonuclease, a tRNA ligase, and a tRNA 2'-phosphotransferase. The tRNA splicing endonuclease, a complex of four different subunits, cleaves pre-tRNA at the 5' and 3' splice sites to release the intron. The products of this cleavage are an intron and two tRNA half-molecules, one bearing a 2',3' cyclic phosphate terminus and the other bearing a 5'-OH terminus [Peebles83]. tRNA ligase covalently joins the two half-molecules through a complex series of ATP-dependent reactions [Westaway88, Belford93, Westaway93]. After ligation, a 2' phosphate remains at the splice junction and is removed by a specific tRNA 2'-phosphotransferase [Culver97].

During the process of tRNA splicing ADP ribose 1'',2''-cyclic phosphate is formed as a by-product. This compound is recycled back to ADP-D-ribose by the action of two enzymes - cyclic phosphodiesterase and ADP-ribose 1''-phosphate phosphatase [Nasr00, Shull05]/

Created 14-Jan-2011 by Caspi R, SRI International


Belford93: Belford HG, Westaway SK, Abelson J, Greer CL (1993). "Multiple nucleotide cofactor use by yeast ligase in tRNA splicing. Evidence for independent ATP- and GTP-binding sites." J Biol Chem 268(4);2444-50. PMID: 8428919

Culver97: Culver GM, McCraith SM, Consaul SA, Stanford DR, Phizicky EM (1997). "A 2'-phosphotransferase implicated in tRNA splicing is essential in Saccharomyces cerevisiae." J Biol Chem 272(20);13203-10. PMID: 9148937

Nasr00: Nasr F, Filipowicz W (2000). "Characterization of the Saccharomyces cerevisiae cyclic nucleotide phosphodiesterase involved in the metabolism of ADP-ribose 1",2"-cyclic phosphate." Nucleic Acids Res 28(8);1676-83. PMID: 10734185

Ogden84: Ogden RC, Lee MC, Knapp G (1984). "Transfer RNA splicing in Saccharomyces cerevisiae: defining the substrates." Nucleic Acids Res 12(24);9367-82. PMID: 6096826

Peebles83: Peebles CL, Gegenheimer P, Abelson J (1983). "Precise excision of intervening sequences from precursor tRNAs by a membrane-associated yeast endonuclease." Cell 32(2);525-36. PMID: 6186398

Shull05: Shull NP, Spinelli SL, Phizicky EM (2005). "A highly specific phosphatase that acts on ADP-ribose 1''-phosphate, a metabolite of tRNA splicing in Saccharomyces cerevisiae." Nucleic Acids Res 33(2);650-60. PMID: 15684411

Westaway88: Westaway SK, Phizicky EM, Abelson J (1988). "Structure and function of the yeast tRNA ligase gene." J Biol Chem 263(7);3171-6. PMID: 3277966

Westaway93: Westaway SK, Belford HG, Apostol BL, Abelson J, Greer CL (1993). "Novel activity of a yeast ligase deletion polypeptide. Evidence for GTP-dependent tRNA splicing." J Biol Chem 268(4);2435-43. PMID: 8428918

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Culver94: Culver GM, Consaul SA, Tycowski KT, Filipowicz W, Phizicky EM (1994). "tRNA splicing in yeast and wheat germ. A cyclic phosphodiesterase implicated in the metabolism of ADP-ribose 1",2"-cyclic phosphate." J Biol Chem 269(40);24928-34. PMID: 7929175

Huh03: Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK (2003). "Global analysis of protein localization in budding yeast." Nature 425(6959);686-91. PMID: 14562095

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Martzen99: Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM (1999). "A biochemical genomics approach for identifying genes by the activity of their products." Science 286(5442);1153-5. PMID: 10550052

Rauhut90: Rauhut R, Green PR, Abelson J (1990). "Yeast tRNA-splicing endonuclease is a heterotrimeric enzyme." J Biol Chem 265(30);18180-4. PMID: 2211694

Reyes88: Reyes VM, Abelson J (1988). "Substrate recognition and splice site determination in yeast tRNA splicing." Cell 55(4);719-30. PMID: 3141064

Trotta97: Trotta CR, Miao F, Arn EA, Stevens SW, Ho CK, Rauhut R, Abelson JN (1997). "The yeast tRNA splicing endonuclease: a tetrameric enzyme with two active site subunits homologous to the archaeal tRNA endonucleases." Cell 89(6);849-58. PMID: 9200603

Xu90: Xu Q, Teplow D, Lee TD, Abelson J (1990). "Domain structure in yeast tRNA ligase." Biochemistry 29(26);6132-8. PMID: 2207062

Yoshihisa03: Yoshihisa T, Yunoki-Esaki K, Ohshima C, Tanaka N, Endo T (2003). "Possibility of cytoplasmic pre-tRNA splicing: the yeast tRNA splicing endonuclease mainly localizes on the mitochondria." Mol Biol Cell 14(8);3266-79. PMID: 12925762

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sun May 1, 2016, biocyc11.