title: Design and Experimental Evolution of trans-Splicing Group I Intron Ribozymes.
abstract: Group I intron ribozymes occur naturally ascis-splicing ribozymes, in the form of introns that do not require the spliceosome for their removal. Instead, they catalyze two consecutivetrans-phosphorylation reactions to remove themselves from a primary transcript, and join the two flanking exons. Designed,trans-splicing variants of these ribozymes replace the 3'-portion of a substrate with the ribozyme's 3'-exon, replace the 5'-portion with the ribozyme's 5'-exon, or insert/remove an internal sequence of the substrate. Two of these designs have been evolved experimentally in cells, leading to variants of group I intron ribozymes that splice more efficiently, recruit a cellular protein to modify the substrate's gene expression, or elucidate evolutionary pathways of ribozymes in cells. Some of the artificial,trans-splicing ribozymes are promising as tools in therapy, and as model systems for RNA evolution in cells. This review provides an overview of the different types oftrans-splicing group I intron ribozymes that have been generated, and the experimental evolution systems that have been used to improve them.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, CA 92093-0356, USA. ufmuller@ucsd.edu.
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Müller
mesh_terms: D019143:Evolution, Molecular; D005818:Genetic Engineering; D007438:Introns; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D012322:RNA Precursors / Q000235:genetics*; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020040:Trans-Splicing
chemical_list: C116167:GIR1 ribozyme; D012322:RNA Precursors; D016337:RNA, Catalytic
keywords: evolution; ribozyme; splicing