title: Modelling translation initiation under the influence of sRNA.
abstract: Bacterial small non-coding RNA (sRNA) plays an important role in post-transcriptional gene regulation. Although the number of annotated sRNA is steadily increasing, their functional characterization is still lagging behind. Various computational strategies for finding sRNA−mRNA interactions, and thus putative sRNA targets, were developed. Most of them suffer from a high false positive rate. Here, we present a qualitative model to simulate the effect of an sRNA on the translation initiation of a potential target. Information about the ribosome−mRNA interaction, sRNA−mRNA interaction and expression information from deep sequencing experiments is integrated to calculate the change in translation initiation complex formation, as a proxy for translational activity. This model can be used to post-evaluate predicted targets, hence condensing the list of potential targets. We show that our translation initiation model, under the influence of an sRNA, can successfully simulate thirteen out of fifteen tested sRNA−mRNA interactions in a qualitative manner. To show the gain in specificity, we applied our method to a target search for the Escherichia coli sRNA RyhB. Compared with simple target prediction without post-evaluation, we reduce the number of targets to less than one fourth potential targets, considerably reducing the burden of experimental validation.
authors.affiliation: Institute for Theoretical Chemistry, University Vienna, Währingerstraße 17, 1090 Vienna, Austria. fabian@tbi.univie.ac.at
authors.forename: Fabian
authors.initials: F
authors.lastname: Amman
authors.forename: Christoph
authors.initials: C
authors.lastname: Flamm
authors.forename: Ivo
authors.initials: I
authors.lastname: Hofacker
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D014176:Protein Biosynthesis / Q000235:genetics*; D012329:RNA, Bacterial / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000502:physiology*
chemical_list: D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D058727:RNA, Small Untranslated