The distributions, mechanisms, and structures of metabolite-binding riboswitches

Jeffrey E Barrick¹^,2 and Ronald R Breaker¹^,3^,4

¹Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8103, USA

²Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI48824-4320, USA

³Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520-8103, USA

⁴Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA

author email corresponding author email

Genome Biology 2007, 8:R239doi:10.1186/gb-2007-8-11-r239


Published:	12 November 2007

Subject areas: Biochemistry and structural biology, Bioinformatics, Evolution

Abstract

Background

Riboswitches are noncoding RNA structures that appropriately regulate genes in response to changing cellular conditions. The expression of many proteins involved in fundamental metabolic processes is controlled by riboswitches that sense relevant small molecule ligands. Metabolite-binding riboswitches that recognize adenosylcobalamin (AdoCbl), thiamin pyrophosphate (TPP), lysine, glycine, flavin mononucleotide (FMN), guanine, adenine, glucosamine-6-phosphate (GlcN6P), 7-aminoethyl 7-deazaguanine (preQ₁), and S-adenosylmethionine (SAM) have been reported.

Results

We have used covariance model searches to identify examples of ten widespread riboswitch classes in the genomes of organisms from all three domains of life. This data set rigorously defines the phylogenetic distributions of these riboswitch classes and reveals how their gene control mechanisms vary across different microbial groups. By examining the expanded aptamer sequence alignments resulting from these searches, we have also re-evaluated and refined their consensus secondary structures. Updated riboswitch structure models highlight additional RNA structure motifs, including an unusual double T-loop arrangement common to AdoCbl and FMN riboswitch aptamers, and incorporate new, sometimes noncanonical, base-base interactions predicted by a mutual information analysis.

Conclusion

Riboswitches are vital components of many genomes. The additional riboswitch variants and updated aptamer structure models reported here will improve future efforts to annotate these widespread regulatory RNAs in genomic sequences and inform ongoing structural biology efforts. There remain significant questions about what physiological and evolutionary forces influence the distributions and mechanisms of riboswitches and about what forms of regulation substitute for riboswitches that appear to be missing in certain lineages.