Methylation at nucleotide G745 or G748 in 23S rRNA distinguishes Gram-negative from Gram-positive bacteria

Autor: Stephen Douthwaite, Mingfu Liu
Rok vydání: 2002
Předmět:
Zdroj: Molecular Microbiology. 44:195-204
ISSN: 1365-2958
0950-382X
Popis: Summary Bacteria tune the function of their ribosomes by methylating specific rRNA nucleotides. Nucleotide G745 in Escherichia coli 23S rRNA is methylated by the methyltransferase enzyme RrmA, whereas in Streptomyces fradiae, the neighbouring nucleotide G748 is methylated by the enzyme TlrB. Both nucleotides line the peptide exit channel of the ribosome at the binding site of macrolide, lincosamide and streptogramin B antibiotics. Resistance to the macrolide tylosin, which is produced by S. fradiae, is conferred by methylation of G748. RrmA and TlrB are homologues (29% identical), and a database search against all presently available sequences revealed a further two dozen homologues from a wide variety of Bacteria. No homologues were found among the Archaea or Eukarya. The bacterial sequences adhere to the species phylogeny and segregate into two groups, in which the Gramnegative sequences align with RrmA and the Gram-positives with TlrB. Consistently, in more than 20 species tested, the distribution of methylation in the Gram-negative rRNAs (methylated at G745) and the Gram-positives (methylated at G748) perfectly matches the bacterial phylogeny. Cloning and ex-pression of representative methyltransferase genes showed that this specificity of methylation is determined solely by the methyltransferase enzyme and is independent of the origin of the rRNA substrate. This is the first case in which the position of an RNA methylation defines a sharp division between the Gram-negative and Gram-positive bacteria. Given the specificities and distribution of these methyltransferases, we propose a change in the nomenclature of RrmA to RlmAI (rRNA large subunit methyltransferase) and of TlrB to RlmAII.
Databáze: OpenAIRE