Fast prediction of RNA-RNA interaction.docVIP

Salarietal.AlgorithmsforMolecularBiology2010,5:5 /content/5/1/5 RESEARCH OpenAccess FastpredictionofRNA-RNAinteraction RahelehSalari1,RolfBackofen2,SCenkSahinalp1* Abstract Background:RegulatoryantisenseRNAsareaclassofncRNAsthatregulategeneexpressionbyprohibitingthe translationofanmRNAbyestablishingstableinteractionswithatargetsequence.Thereisgreatdemandfor efficientcomputationalmethodstopredictthespecificinteractionbetweenanncRNAanditstargetmRNA(s). Thereareanumberofalgorithmsintheliteraturewhichcanpredictavarietyofsuchinteractions-unfortunately ataveryhighcomputationalcost.Althoughsomeexistingtargetpredictionapproachesaremuchfaster,theyare specializedforinteractionswithasinglebindingsite. Methods:Inthispaperwepresentanovelalgorithmtoaccuratelypredicttheminimumfreeenergystructureof RNA-RNAinteractionunderthemostgeneraltypeofinteractionsstudiedintheliterature.Moreover,weintroduce afastheuristicmethodtopredictthespecific(multiple)bindingsitesoftwointeractingRNAs. Results:Weverifytheperformanceofouralgorithmsforjointstructureandbindingsitepredictiononasetof knowninteractingRNApairs.Experimentalresultsshowouralgorithmsarehighlyaccurateandoutperformall competitiveapproaches. Background weuseisthejointstructureenergymodelrecentlypre- Regulatorynon-codingRNAs(ncRNAs)playanimpor- sented byChitsaz etal. [2] which ismoregeneral than tantroleingeneregulation.Studiesonbothprokaryotic theoneusedbyAlkanetal. and eukaryotic cells show that such ncRNAs usually Inwhatfollowsbelow,wefirstdescribeacombinator- bindtotheirtargetmRNAtoregulatethetranslationof ialalgorithmtocomputetheminimumfreeenergyjoint corresponding genes. Many regulatory RNAs such as structure formed by two interacting RNAs. This algo- microRNAs and small interfering RNAs (miRNAs/siR- rithmhasarunningtimeofO(n6)andusesO(n4 )space NAs)areveryshortandhavefullsequencecomplemen- - which makes it impractical for long RNA molecules. tarity to the targets. However some of the regulatory Then we pre