{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:53:54Z","timestamp":1791050034363,"version":"4.1.0"},"reference-count":40,"publisher":"Cold Spring Harbor Laboratory","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["RNA"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>The <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>-(isopentenyl)adenosine (i<jats:sup>6<\/jats:sup>A) modification of some tRNAs at position A37 is found in all kingdoms and facilitates codon-specific mRNA decoding, but occurs in different subsets of tRNAs in different species. Here we examine yeasts' tRNA isopentenyltransferases (i.e., dimethylallyltransferase, DMATase, members of the \u0394<jats:sup>2<\/jats:sup>-isopentenylpyrophosphate transferase, IPPT superfamily) encoded by <jats:italic>tit1<jats:sup>+<\/jats:sup><\/jats:italic> in <jats:italic>Schizosaccharomyces pombe<\/jats:italic> and MOD5 in <jats:italic>Saccharomyces cerevisiae<\/jats:italic>, whose homologs are <jats:italic>Escherichia coli<\/jats:italic> miaA, the human tumor suppressor TRIT1, and the <jats:italic>Caenorhabditis elegans<\/jats:italic> life-span gene product GRO-1. A major determinant of miaA activity is known to be the single-stranded tRNA sequence, A36A37A38, in a stem\u2013loop. tRNA<jats:sup>Trp<\/jats:sup><jats:sub>CCA<\/jats:sub> from either yeast is a Tit1p substrate, but neither is a Mod5p substrate despite the presence of A36A37A38. We show that Tit1p accommodates a broader range of substrates than Mod5p. tRNA<jats:sup>Trp<\/jats:sup><jats:sub>CCA<\/jats:sub> is distinct from Mod5p substrates, which we sort into two classes based on the presence of G at position 34 and other elements. A single substitution of C34 to G converts tRNA<jats:sup>Trp<\/jats:sup><jats:sub>CCA<\/jats:sub> to a Mod5p substrate in vitro and in vivo, consistent with amino acid contacts to G34 in existing Mod5p-tRNA<jats:sup>Cys<\/jats:sup><jats:sub>GCA<\/jats:sub> crystal structures. Mutation of Mod5p in its G34 recognition loop region debilitates it differentially for its G34 (class I) substrates. Multiple alignments reveal that the G34 recognition loop sequence of Mod5p differs significantly from Tit1p, which more resembles human TRIT1 and other DMATases. We show that TRIT1 can also modify tRNA<jats:sup>Trp<\/jats:sup><jats:sub>CCA<\/jats:sub> consistent with broad recognition similar to Tit1p. This study illustrates previously unappreciated molecular plasticity and biological diversity of the tRNA-isopentenyltransferase system of eukaryotes.<\/jats:p>","DOI":"10.1261\/rna.2628611","type":"journal-article","created":{"date-parts":[[2011,8,27]],"date-time":"2011-08-27T05:02:14Z","timestamp":1314421334000},"page":"1846-1857","source":"Crossref","is-referenced-by-count":55,"title":["Plasticity and diversity of tRNA anticodon determinants of substrate recognition by eukaryotic A37 isopentenyltransferases"],"prefix":"10.1261","volume":"17","author":[{"given":"Tek N.","family":"Lamichhane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan H.","family":"Blewett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Maraia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2011,8,26]]},"reference":[{"key":"2021112105513817000_17.10.1846.1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.104"},{"key":"2021112105513817000_17.10.1846.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.11.046"},{"key":"2021112105513817000_17.10.1846.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.09.021"},{"key":"2021112105513817000_17.10.1846.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.61"},{"key":"2021112105513817000_17.10.1846.5","doi-asserted-by":"crossref","unstructured":"Bjork GR . 1995. Biosynthesis and function of modified nucleosides. In tRNA: Structure, biosynthesis, and function (ed. D Soll, UL Rajbhandary), pp. 165\u2013205. ASM Press, Washington, DC.","DOI":"10.1128\/9781555818333.ch11"},{"key":"2021112105513817000_17.10.1846.6","doi-asserted-by":"publisher","DOI":"10.1021\/bi900337d"},{"key":"2021112105513817000_17.10.1846.7","doi-asserted-by":"crossref","unstructured":"Daugeron MC , Lenstra TL , Frizzarin M , El Yacoubi B , Liu X , Baudin-Baillieu A , Lijnzaad P , Decourty L , Saveanu C , Jacquier A , . 2011. Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC\/KEOPS in the t6A modification of tRNAs. Nucleic Acids Res doi: 10.1093\/nar\/gkr178.","DOI":"10.1093\/nar\/gkr178"},{"key":"2021112105513817000_17.10.1846.8","first-page":"177","article-title":"Isolation and characterization of MOD5, a gene required for isopentenylation of cytoplasmic and mitochondrial tRNAs of Saccharomyces cerevisiae","volume":"7","year":"1987","journal-title":"Mol Cell Biol"},{"key":"2021112105513817000_17.10.1846.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.14.120180.000453"},{"key":"2021112105513817000_17.10.1846.10","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp152"},{"key":"2021112105513817000_17.10.1846.11","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.363"},{"key":"2021112105513817000_17.10.1846.12","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)90697-5"},{"key":"2021112105513817000_17.10.1846.13","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(79)90349-0"},{"key":"2021112105513817000_17.10.1846.14","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(69)90583-X"},{"key":"2021112105513817000_17.10.1846.15","first-page":"2382","article-title":"MOD5 translation initiation sites determine N\n               6-isopentenyladenosine modification of mitochondrial and cytoplasmic tRNA","volume":"11","year":"1991","journal-title":"Mol Cell Biol"},{"key":"2021112105513817000_17.10.1846.16","doi-asserted-by":"publisher","DOI":"10.1042\/bj1530437"},{"key":"2021112105513817000_17.10.1846.17","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.2.621-636.2005"},{"key":"2021112105513817000_17.10.1846.18","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1110"},{"key":"2021112105513817000_17.10.1846.19","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(80)90305-8"},{"key":"2021112105513817000_17.10.1846.20","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1790"},{"key":"2021112105513817000_17.10.1846.21","doi-asserted-by":"crossref","unstructured":"Johansson MJ , Bystrom AS . 2005. Transfer RNA modifications and modifying enzymes in Saccharomyces cerevisiae . In Topics in current genetics: Fine-tuning of RNA functions by modification and editing (ed. Grosjean H ), pp. 88\u2013120. Springer-Verlag, Berlin, Heidelberg.","DOI":"10.1007\/b105814"},{"key":"2021112105513817000_17.10.1846.22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn772"},{"key":"2021112105513817000_17.10.1846.23","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(71)80171-0"},{"key":"2021112105513817000_17.10.1846.24","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/S0021-9258(17)37806-7","article-title":"Characterization of a UGA-suppressing serine tRNA from Schizosaccharomyces pombe with the help of a new in vitro assay system for eukaryotic suppressor tRNAs","volume":"254","year":"1979","journal-title":"J Biol Chem"},{"key":"2021112105513817000_17.10.1846.25","doi-asserted-by":"crossref","unstructured":"Kohli J , Munz P , Soll D . 1989. 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