Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria

Keith A Corbino¹ , Jeffrey E Barrick² , Jinsoo Lim¹ , Rüdiger Welz¹^,3 , Brian J Tucker² , Izabela Puskarz¹ , Maumita Mandal¹^,4 , Noam D Rudnick¹ and Ronald R Breaker¹

¹Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520-8103, USA

²Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208103, New Haven, CT 06520-8103, USA

³Department of Chemistry, Yale University, P.O. Box 208103, New Haven, CT 06520-8103, USA

⁴Department of Physics, University of California, Berkeley, CA 94720-7200, USA

author email corresponding author email

Genome Biology 2005, 6:R70doi:10.1186/gb-2005-6-8-r70


Published:	1 August 2005

Subject areas: Biochemistry and structural biology, Microbiology and parasitology, Genome studies, Molecular biology

Abstract

Background

Riboswitches are RNA elements in the 5' untranslated leaders of bacterial mRNAs that directly sense the levels of specific metabolites with a structurally conserved aptamer domain to regulate expression of downstream genes. Riboswitches are most common in the genomes of low GC Gram-positive bacteria (for example, Bacillus subtilis contains examples of all known riboswitches), and some riboswitch classes seem to be restricted to this group.

Results

We used comparative sequence analysis and structural probing to identify five RNA elements (serC, speF, suhB, ybhL, and metA) that reside in the intergenic regions of Agrobacterium tumefaciens and many other α-proteobacteria. One of these, the metA motif, is found upstream of methionine biosynthesis genes and binds S-adenosylmethionine (SAM). This natural aptamer most likely functions as a SAM riboswitch (SAM-II) with a consensus sequence and structure that is distinct from the class of SAM riboswitches (SAM-I) predominantly found in Gram-positive bacteria. The minimal functional SAM-II aptamer consists of fewer than 70 nucleotides, which form a single stem and a pseudoknot. Despite its simple architecture and lower affinity for SAM, the SAM-II aptamer strongly discriminates against related compounds.

Conclusion

SAM-II is the only metabolite-binding riboswitch class identified so far that is not found in Gram-positive bacteria, and its existence demonstrates that biological systems can use multiple RNA structures to sense a single chemical compound. The two SAM riboswitches might be 'RNA World' relics that were selectively retained in certain bacterial lineages or new motifs that have emerged since the divergence of the major bacterial groups.