Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA

Nucleic Acids Res. 2013 Jan;41(2):1151-63. doi: 10.1093/nar/gks1102. Epub 2012 Nov 23.


Ribosomal RNA undergoes various modifications to optimize ribosomal structure and expand the topological potential of RNA. The most common nucleotide modifications in ribosomal RNA (rRNA) are pseudouridylations and 2'-O methylations (Nm), performed by H/ACA box snoRNAs and C/D box snoRNAs, respectively. Furthermore, rRNAs of both ribosomal subunits also contain various base modifications, which are catalysed by specific enzymes. These modifications cluster in highly conserved areas of the ribosome. Although most enzymes catalysing 18S rRNA base modifications have been identified, little is known about the 25S rRNA base modifications. The m(1)A modification at position 645 in Helix 25.1 is highly conserved in eukaryotes. Helix formation in this region of the 25S rRNA might be a prerequisite for a correct topological framework for 5.8S rRNA to interact with 25S rRNA. Surprisingly, we have identified ribosomal RNA processing protein 8 (Rrp8), a nucleolar Rossman-fold like methyltransferase, to carry out the m(1)A base modification at position 645, although Rrp8 was previously shown to be involved in A2 cleavage and 40S biogenesis. In addition, we were able to identify specific point mutations in Rrp8, which show that a reduced S-adenosyl-methionine binding influences the quality of the 60S subunit. This highlights the dual functionality of Rrp8 in the biogenesis of both subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein O-Methyltransferase
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / metabolism*
  • Ribonucleoproteins, Small Nucleolar / genetics
  • Ribonucleoproteins, Small Nucleolar / metabolism
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • S-Adenosylmethionine / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Deletion


  • Nuclear Proteins
  • RNA, Ribosomal
  • Ribonucleoproteins, Small Nucleolar
  • Saccharomyces cerevisiae Proteins
  • RNA, ribosomal, 25S
  • GAR1 protein, S cerevisiae
  • 1-methyladenine
  • S-Adenosylmethionine
  • Methyltransferases
  • Protein O-Methyltransferase
  • RRP8 protein, S cerevisiae
  • Adenine