title: Structure and mechanism of a metal-sensing regulatory RNA.
abstract: Organisms maintain the correct balance of intracellular metals primarily through metal-sensing proteins that control transport and storage of the target ion(s). Here, we reveal the basis of metal sensing and genetic control by a metalloregulatory RNA. Our data demonstrate that a previously uncharacterized orphan riboswitch, renamed the "M-box," is a divalent metal-sensing RNA involved in Mg(2+) homeostasis. A combination of genetic, biochemical, and biophysical techniques demonstrate that Mg(2+) induces a compacted tertiary architecture for M-box RNAs that regulates the accessibility of nucleotides involved in genetic control. Molecular details are provided by crystallographic structure determination of a Mg(2+)-bound M-box RNA. Given the distribution of this RNA element, it may constitute a common mode for bacterial metal ion regulation, and its discovery suggests the possibility of additional RNA-based metal sensors in modern and primordial organisms.
authors.affiliation: Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Dann
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Wakeman
authors.forename: Cecelia L
authors.initials: CL
authors.lastname: Sieling
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Baker
authors.forename: Irnov
authors.initials: I
authors.lastname: Irnov
authors.forename: Wade C
authors.initials: WC
authors.lastname: Winkler
mesh_terms: D020121:5' Untranslated Regions; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D003461:Crystallography; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006706:Homeostasis; D007763:Lac Operon; D015636:Magnesium Chloride / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D014158:Transcription, Genetic