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Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity

2013; Oxford University Press; Volume: 41; Issue: 20 Linguagem: Inglês

10.1093/nar/gkt702

1362-4962

John Laver, Xiao Li, Kristin Ancevicius, J. Timothy Westwood, Craig A. Smibert, Quaid Morris, Howard D. Lipshitz,

RNA modifications and cancer

Despite studies that have investigated the interactions of double-stranded RNA-binding proteins like Staufen with RNA in vitro, how they achieve target specificity in vivo remains uncertain.We performed RNA co-immunoprecipitations followed by microarray analysis to identify Staufen-associated mRNAs in early Drosophila embryos.Analysis of the localization and functions of these transcripts revealed a number of potentially novel roles for Staufen.Using computational methods, we identified two sequence features that distinguish Staufen's target transcripts from non-targets.First, these Drosophila transcripts, as well as those human transcripts bound by human Staufen1 and 2, have 3 0 untranslated regions (UTRs) that are 3-4fold longer than unbound transcripts.Second, the 3 0 UTRs of Staufen-bound transcripts are highly enriched for three types of secondary structures.These structures map with high precision to previously identified Staufen-binding regions in Drosophila bicoid and human ARF1 3 0 UTRs.Our results provide the first systematic genome-wide analysis showing how a double-stranded RNAbinding protein achieves target specificity.