Biosynthesis of wyosine derivatives in tRNA(Phe) of Archaea: role of a remarkable bifunctional tRNA(Phe):m1G/imG2 methyltransferase

RNA. 2014 Jun;20(6):747-53. doi: 10.1261/rna.043315.113.


The presence of tricyclic wyosine derivatives 3'-adjacent to anticodon is a hallmark of tRNA(Phe) in eukaryotes and archaea. In yeast, formation of wybutosine (yW) results from five enzymes acting in a strict sequential order. In archaea, the intermediate compound imG-14 (4-demethylwyosine) is a target of three different enzymes, leading to the formation of distinct wyosine derivatives (yW-86, imG, and imG2). We focus here on a peculiar methyltransferase (aTrm5a) that catalyzes two distinct reactions: N(1)-methylation of guanosine and C(7)-methylation of imG-14, whose function is to allow the production of isowyosine (imG2), an intermediate of the 7-methylwyosine (mimG) biosynthetic pathway. Based on the formation of mesomeric forms of imG-14, a rationale for such dual enzymatic activities is proposed. This bifunctional tRNA:m(1)G/imG2 methyltransferase, acting on two chemically distinct guanosine derivatives located at the same position of tRNA(Phe), is unique to certain archaea and has no homologs in eukaryotes. This enzyme here referred to as Taw22, probably played an important role in the emergence of the multistep biosynthetic pathway of wyosine derivatives in archaea and eukaryotes.

Keywords: COG2520; archaea; methyltransferase; modification; transfer RNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticodon / genetics
  • Archaea / genetics*
  • Archaea / metabolism
  • Biosynthetic Pathways / genetics*
  • Guanosine / analogs & derivatives*
  • Guanosine / biosynthesis
  • Guanosine / genetics
  • Guanosine / metabolism
  • Nucleosides / genetics
  • Nucleosides / metabolism
  • RNA, Transfer, Phe / biosynthesis*
  • RNA, Transfer, Phe / genetics
  • RNA, Transfer, Phe / metabolism
  • tRNA Methyltransferases / biosynthesis*
  • tRNA Methyltransferases / genetics
  • tRNA Methyltransferases / metabolism


  • Anticodon
  • Nucleosides
  • RNA, Transfer, Phe
  • wybutosine
  • Guanosine
  • wyosine
  • tRNA Methyltransferases