A Widespread Riboswitch Candidate That Controls Bacterial Genes Involved in Molybdenum Cofactor and Tungsten Cofactor Metabolism

摘要

Riboswitches are ligand-binding RNA domains usually found in theuntranslated regions (UTRs) of eubacterial mRNAs. These conserved RNAdomains consist of an aptamer region that binds the ligands and an expres-sion platform which regulates expression of adjacent genes under allostericcontrol of the ligand binding site (Fig. 1). Regulatory ligands are eitherproducts, coenzymes, or cofactors of the biochemical pathways they regu-late. This study used bioinformatics to search for riboswitches with similarstructural motifs and functions, with a focus on the molybdenum-containingcofactor (Moco)-binding RNA domain. Moco, a tricyclic pyranopterin con-taining a coordinated molybdenum atom, is present in the active sites ofnumerous enzymes that use the redox activity of Mo to catalyze reactions inthe carbon, nitrogen, and sulfur metabolic cycles. The comparative genom-ics search yielded 176 representative structures which showed similar sec-ondary motifs called Moco RNAs whose sequences were 75% to 100%conserved. Biochemical and genetic experiments determined that, forEscherichia coli, its Moco RNA representative functions as a Moco-sensingriboswitch regulating molybdenum metabolism, biosynthesis of Mo-depen-dent enzymes, and Mo transport. The study further showed that recognitionof Moco is specific and concentration dependent and that expression ofgenes regulated by this region is a function of changing conditions in thecell. A variant of Moco RNA lacking a particular stem (P3), however, couldbind tungsten cofactor (tungsten) at its ligand binding site regulating genesfor Tuco metabolism as well.