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Nucleic Acids Research 2005 33(18):6057-6069; doi:10.1093/nar/gki911
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Published online 27 October 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs

Uri Laserson1,2, Hin Hark Gan1 and Tamar Schlick1,2,*

1Department of Chemistry, New York University 251 Mercer Street, New York, NY 10012, USA 2Courant Institute of Mathematical Sciences, New York University 251 Mercer Street, New York, NY 10012, USA

*To whom correspondence should be addressed. Tel: +1 212 998 3116; Fax: +1 212 998 4152; E-mail: schlick{at}nyu.edu

Received August 5, 2005. Revised October 3, 2005. Accepted October 3, 2005.

Riboswitches and RNA interference are important emerging mechanisms found in many organisms to control gene expression. To enhance our understanding of such RNA roles, finding small regulatory motifs in genomes presents a challenge on a wide scale. Many simple functional RNA motifs have been found by in vitro selection experiments, which produce synthetic target-binding aptamers as well as catalytic RNAs, including the hammerhead ribozyme. Motivated by the prediction of Piganeau and Schroeder [(2003) Chem. Biol., 10, 103–104] that synthetic RNAs may have natural counterparts, we develop and apply an efficient computational protocol for identifying aptamer-like motifs in genomes. We define motifs from the sequence and structural information of synthetic aptamers, search for sequences in genomes that will produce motif matches, and then evaluate the structural stability and statistical significance of the potential hits. Our application to aptamers for streptomycin, chloramphenicol, neomycin B and ATP identifies 37 candidate sequences (in coding and non-coding regions) that fold to the target aptamer structures in bacterial and archaeal genomes. Further energetic screening reveals that several candidates exhibit energetic properties and sequence conservation patterns that are characteristic of functional motifs. Besides providing candidates for experimental testing, our computational protocol offers an avenue for expanding natural RNA's functional repertoire.

Present address Uri Laserson, Department of Mathematics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA


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