Nucleic Acids Research Advance Access first published online on April 30, 2009
This version published online on May 11, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp271
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One RNA plays three roles to provide catalytic activity to a group I intron lacking an endogenous internal guide sequence
Department of Chemistry, Portland State University, PO Box 751, Portland, OR 97207, USA
*To whom correspondence should be addressed. Tel: +1 503 725 8769; Fax: +1 503 725 9525; Email: niles{at}pdx.edu
Received January 16, 2009. Revised March 31, 2009. Accepted April 10, 2009.
Catalytic RNA molecules possess simultaneously a genotype and a phenotype. However, a single RNA genotype has the potential to adopt two or perhaps more distinct phenotypes as a result of differential folding and/or catalytic activity. Such multifunctionality would be particularly significant if the phenotypes were functionally inter-related in a common biochemical pathway. Here, this phenomenon is demonstrated by the ability of the Azoarcus group I ribozyme to function when its canonical internal guide sequence (GUG) has been removed from the 5' end of the molecule, and added back exogenously in trans. The presence of GUG triplets in non-covalent fragments of the ribozyme allow trans-splicing to occur in both a reverse splicing assay and a covalent self-assembly assay in which the internal guide sequence (IGS)-less ribozyme can put itself together from two of its component pieces. Analysis of these reactions indicates that a single RNA fragment can perform up to three distinct roles in a reaction: behaving as a portion of a catalyst, behaving as a substrate, and providing an exogenous IGS. This property of RNA to be multifunctional in a single reaction pathway bolsters the probability that a system of self-replicating molecules could have existed in an RNA world during the origins of life on the Earth.