title: Base ionization and ligand binding: how small ribozymes and riboswitches gain a foothold in a protein world.
abstract: Genome sequencing has produced thousands of nonprotein coding (nc)RNA sequences including new ribozymes and riboswitches. Such RNAs are notable for their extraordinary functionality, which entails exquisite folding that culminates in biocatalytic or ligand-binding capabilities. Here we discuss advances in relating ncRNA form to function with an emphasis on base pK(a) shifting by the hairpin and hepatitis delta virus ribozymes. We then describe ligand binding by the two smallest riboswitches, which target preQ(1) and S-adenosyl-(l)-homocysteine, followed by an analysis of a second-messenger riboswitch that binds cyclic-di-GMP. Each riboswitch is then compared to a protein that binds the same ligand to contrast binding properties. The results showcase the breadth of functionality attainable from ncRNAs, as well as molecular features notable for antibacterial design.
authors.affiliation: Department of Biochemistry and Biophysics, and Center for RNA Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Liberman
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Wedekind
mesh_terms: D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006860:Hydrogen Bonding; D008024:Ligands; D008670:Metals / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058928:Riboswitch / Q000235:genetics / Q000502:physiology*; D015290:Second Messenger Systems / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D008670:Metals; D016337:RNA, Catalytic; D058928:Riboswitch; C418481:hairpin ribozyme; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP