Inhibition of Poly(A)-Binding Protein with a Synthetic RNA Mimic Reduces Pain Sensitization in Mice

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dc.contributor.ORCID0000-0002-6971-6221 (Price, TJ)en_US
dc.contributor.ORCID0000-0002-3768-6996 (Campbell, ZT)en_US
dc.contributor.authorBarragan-Iglesias, Paulinoen_US
dc.contributor.authorLou, Tzu-Fangen_US
dc.contributor.authorBhat, Vandita D.en_US
dc.contributor.authorMegat, Salimen_US
dc.contributor.authorBurton, Michael D.en_US
dc.contributor.authorPrice, Theodore J.en_US
dc.contributor.authorCampbell, Zachary T.en_US
dc.contributor.utdAuthorBarragan-Iglesias, Paulinoen_US
dc.contributor.utdAuthorLou, Tzu-Fangen_US
dc.contributor.utdAuthorBhat, Vandita D.en_US
dc.contributor.utdAuthorMegat, Salimen_US
dc.contributor.utdAuthorBurton, Michael D.en_US
dc.contributor.utdAuthorPrice, Theodore J.en_US
dc.contributor.utdAuthorCampbell, Zachary T.en_US
dc.date.accessioned2018-10-22T20:08:38Z
dc.date.available2018-10-22T20:08:38Z
dc.date.created2018-01-02en_US
dc.date.issued2018-10-22
dc.description.abstractNociceptors rely on cap-dependent translation to rapidly induce protein synthesis in response to pro-inflammatory signals. Comparatively little is known regarding the role of the regulatory factors bound to the 3' end of mRNA in nociceptor sensitization. Poly(A)-binding protein (PABP) stimulates translation initiation by bridging the Poly(A) tail to the eukaryotic initiation factor 4F complex associated with the mRNA cap. Here, we use unbiased assessment of PABP binding specificity to generate a chemically modified RNA-based competitive inhibitor of PABP. The resulting RNA mimic, which we designated as the Poly(A) SPOT-ON, is more stable than unmodified RNA and binds PABP with high affinity and selectivity in vitro. We show that injection of the Poly(A) SPOT-ON at the site of an injury can attenuate behavioral response to pain. Collectively, these results suggest that PABP is integral for nociceptive plasticity. The general strategy described here provides a broad new source of mechanism-based inhibitors for RNA-binding proteins and is applicable for in vivo studies.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.departmentSchool of Behavioral and Brain Sciencesen_US
dc.description.sponsorship"National Institutes of Health Grants R01NS100788 (to Z.T.C.), R01GM102575 (to T.J.P.), R01NS065926 (to T.J.P.), The University of Texas STARS program research support grant (to T.J.P.), and the postdoctoral Conacyt fellowship 274414 (to P.B.-I.).en_US
dc.identifier.bibliographicCitationBarragan-Iglesias, Paulino, Tzu-Fang Lou, Vandita D. Bhat, Salim Megat, et al. 2018. "Inhibition of Poly(A)-binding protein with a synthetic RNA mimic reduces pain sensitization in mice." Nature Communications 9(1), doi:10.1038/s41467-017-02449-5en_US
dc.identifier.issn2041-1723en_US
dc.identifier.issue1en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6240
dc.identifier.volume9en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urihttp://dx.doi.org/10.1038/s41467-017-02449-5
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNature Communications
dc.subjectCPEB-3 protein, humanen_US
dc.subjectMessenger RNAen_US
dc.subjectProtein bindingen_US
dc.subjectNeuroplasticityen_US
dc.subjectOligonucleotides, Antisenseen_US
dc.subjectNociceptorsen_US
dc.subjectGene expressionen_US
dc.titleInhibition of Poly(A)-Binding Protein with a Synthetic RNA Mimic Reduces Pain Sensitization in Miceen_US
dc.type.genrearticleen_US

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