A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes

Abstract

Large-scale sequencing of bacterial genomes has opened a new era in computational genomics. Gene complements are successfully analysed on the protein level. However, it has been noted that regulatory sites are less conserved than genes 1 Overbeek R. et al. The use of gene clusters to infer functional coupling. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 2896-2901 Crossref PubMed Scopus (979) Google Scholar , although it is possible to use genomic comparisons in order to predict gene regulation at the level of DNA ( 2 Mironov A.A. et al. Computer analysis of transcription regulatory patterns in completely sequenced bacterial genomes. Nucleic Acids Res. 1999; 27: 2981-2989 Crossref PubMed Scopus (120) Google Scholar ) and RNA ( 3 Vitreschak A. et al. Computer analysis of regulatory patterns in complete bacterial genomes. Translation initiation of the ribosomal protein operons. Biophysics. 1999; (in press) Google Scholar , 4 Huynen M.A. Bork P. Measuring genome evolution. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 5849-5856 Crossref PubMed Scopus (356) Google Scholar ). Indeed, comparative analysis is one of the standard methods to predict the secondary structure of RNA. It has been used to determine the spatial structure of stable RNAs ( 5 Winker S. et al. Structure detection through automated covariance search. Comput. Appl. Biosci. 1990; 6: 365-371 PubMed Google Scholar , 6 Gutell R. et al. Identifying constraints on the higher-order structure of RNA: continued development and application of comparative sequence analysis methods. Nucleic Acids Res. 1992; 20: 5785-5795 Crossref PubMed Scopus (228) Google Scholar , 7 Eddy S.R. Durbin R. RNA sequence analysis using covariance models. Nucleic Acids Res. 1994; 22: 2079-2088 Crossref PubMed Scopus (572) Google Scholar ), and to analyse regulatory RNAs, mostly in viral genomes 8 Le S-Y. Zuker M. Common structures of the 5′ non-coding RNA in enteroviruses and rhinoviruses. Thermodynamical stability and statistical significance. J. Mol. Biol. 1990; 216: 729-741 Crossref PubMed Scopus (83) Google Scholar , 9 Le S.Y. et al. Unusual folding regions and ribosome landing pad within hepatitis C virus and pestivirus RNAs. Gene. 1995; 154: 137-143 Crossref PubMed Scopus (43) Google Scholar . In such studies, either the common fold is selected among many predicted suboptimal folds for a set of RNAs ( 8 Le S-Y. Zuker M. Common structures of the 5′ non-coding RNA in enteroviruses and rhinoviruses. Thermodynamical stability and statistical significance. J. Mol. Biol. 1990; 216: 729-741 Crossref PubMed Scopus (83) Google Scholar ), or analysis of complementary substitutions in aligned sequences is used to construct a single conserved structure 7 Eddy S.R. Durbin R. RNA sequence analysis using covariance models. Nucleic Acids Res. 1994; 22: 2079-2088 Crossref PubMed Scopus (572) Google Scholar , 9 Le S.Y. et al. Unusual folding regions and ribosome landing pad within hepatitis C virus and pestivirus RNAs. Gene. 1995; 154: 137-143 Crossref PubMed Scopus (43) Google Scholar . Non-viral regulatory RNA elements, such as iron-responsive elements 10 Dandekar T. et al. Systematic genomic screening and analysis of mRNA in untranslated regions and mRNA precursors: combining experimental and computational approaches. Bioinformatics. 1999; 14: 271-278 Crossref Scopus (25) Google Scholar , and sites that regulate the initiation of translation in operons of ribosomal proteins 3 Vitreschak A. et al. Computer analysis of regulatory patterns in complete bacterial genomes. Translation initiation of the ribosomal protein operons. Biophysics. 1999; (in press) Google Scholar , 4 Huynen M.A. Bork P. Measuring genome evolution. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 5849-5856 Crossref PubMed Scopus (356) Google Scholar , 11 Keener J. Nomura M. Neidhardt F.C. E. coli and Salmonella. ASM Press, 1996: 1417-1431 Google Scholar often involve conserved structural elements and conserved nucleotides.