title: Unwinding the twister ribozyme: from structure to mechanism.
abstract: The twister ribozyme motif has been identified by bioinformatic means very recently. Currently, four crystal structures with ordered active sites together with a series of chemical and biochemical data provide insights into how this RNA accomplishes its efficient self-cleavage. Of particular interest for a mechanistic proposal are structural distinctions observed in the active sites that concern the conformation of the U-A cleavage site dinucleotide (in-line alignment of the attacking 2'-O nucleophile to the to-be-cleaved PO5' bond versus suboptimal alignments) as well as the presence/absence of Mg2+ions at the scissile phosphate. All structures support the notion that an active site guanine and the conserved adenine at the cleavage site are important contributors to cleavage chemistry, likely being involved in general acid base catalysis. Evidence for innersphere coordination of a Mg2+ion to the pro-S nonbridging oxygen of the scissile phosphate stems from two of the four crystal structures. Together with the finding of thio/rescue effects for phosphorothioate substrates, this suggests the participation of divalent ions in the overall catalytic strategy employed by twister ribozymes. In this context, it is notable that twister retains wild-type activity when the phylogenetically conserved stem P1 is deleted, able to cleave a single nucleotide only. WIREs RNA 2017, 8:e1402. doi: 10.1002/wrna.1402 For further resources related to this article, please visit the WIREs website.
authors.affiliation: Institute of Organic Chemistry, Leopold-Franzens University and Center of Molecular Biosciences Innsbruck CMBI, Innsbruck, Austria.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gebetsberger
authors.affiliation: Institute of Organic Chemistry, Leopold-Franzens University and Center of Molecular Biosciences Innsbruck CMBI, Innsbruck, Austria.
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
mesh_terms: D000818:Animals; D002384:Catalysis; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016337:RNA, Catalytic