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Molecules 2017, 22(1), 75;

Design and Experimental Evolution of trans-Splicing Group I Intron Ribozymes

Department of Chemistry & Biochemistry, University of California, San Diego, CA 92093-0356, USA
Received: 28 September 2016 / Revised: 27 December 2016 / Accepted: 29 December 2016 / Published: 2 January 2017
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Group I intron ribozymes occur naturally as cis-splicing ribozymes, in the form of introns that do not require the spliceosome for their removal. Instead, they catalyze two consecutive trans-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 of trans-splicing group I intron ribozymes that have been generated, and the experimental evolution systems that have been used to improve them. View Full-Text
Keywords: ribozyme; evolution; splicing ribozyme; evolution; splicing

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Müller, U.F. Design and Experimental Evolution of trans-Splicing Group I Intron Ribozymes. Molecules 2017, 22, 75.

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