Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs

Uri Laserson, Hin Hark Gan, Tamar Schlick

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6057-6069
Number of pages13
JournalNucleic Acids Research
Volume33
Issue number18
DOIs
StatePublished - 2005

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Nucleotide Motifs
Genome
RNA
Archaeal Genome
Framycetin
Riboswitch
Bacterial Genomes
Catalytic RNA
Streptomycin
Chloramphenicol
RNA Interference
Adenosine Triphosphate
Gene Expression

ASJC Scopus subject areas

  • Genetics

Cite this

Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs. / Laserson, Uri; Gan, Hin Hark; Schlick, Tamar.

In: Nucleic Acids Research, Vol. 33, No. 18, 2005, p. 6057-6069.

Research output: Contribution to journalArticle

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