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dc.contributor.authorKraushar, Matthew L
dc.contributor.authorThompson, Kevin
dc.contributor.authorWijeratne, H R Sagara
dc.contributor.authorViljetic, Barbara
dc.contributor.authorSakers, Kristina
dc.contributor.authorMarson, Justin W
dc.contributor.authorKontoyiannis, Dimitris L
dc.contributor.authorBuyske, Steven
dc.contributor.authorHart, Ronald P
dc.contributor.authorRasin, Mladen-Roko
dc.date.accessioned2023-03-03T19:26:03Z
dc.date.available2023-03-03T19:26:03Z
dc.date.issued2014-08-25
dc.identifier.citationKraushar ML, Thompson K, Wijeratne HR, Viljetic B, Sakers K, Marson JW, Kontoyiannis DL, Buyske S, Hart RP, Rasin MR. Temporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):E3815-24. doi: 10.1073/pnas.1408305111. Epub 2014 Aug 25. PMID: 25157170; PMCID: PMC4246959.en_US
dc.identifier.eissn1091-6490
dc.identifier.doi10.1073/pnas.1408305111
dc.identifier.pmid25157170
dc.identifier.urihttp://hdl.handle.net/20.500.12648/8477
dc.description.abstractPrecise spatiotemporal control of mRNA translation machinery is essential to the development of highly complex systems like the neocortex. However, spatiotemporal regulation of translation machinery in the developing neocortex remains poorly understood. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of initiation and elongation factors in the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some HuR-dependent proteins, the association with polysomes likewise depends on the eukaryotic initiation factor 2 alpha kinase 4, which associates with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR before embryonic day 10 disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity.
dc.language.isoenen_US
dc.relation.urlhttps://www.pnas.org/doi/10.1073/pnas.1408305111en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectElaven_US
dc.subjectGCN2en_US
dc.subjectposttranscriptional regulationen_US
dc.subjectprofilingen_US
dc.subjectribosomeen_US
dc.titleTemporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.source.volume111
dc.source.issue36
dc.source.beginpageE3815
dc.source.endpage24
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.description.versionVoRen_US
refterms.dateFOA2023-03-03T19:26:04Z
html.description.abstractPrecise spatiotemporal control of mRNA translation machinery is essential to the development of highly complex systems like the neocortex. However, spatiotemporal regulation of translation machinery in the developing neocortex remains poorly understood. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of initiation and elongation factors in the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some HuR-dependent proteins, the association with polysomes likewise depends on the eukaryotic initiation factor 2 alpha kinase 4, which associates with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR before embryonic day 10 disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity.
dc.description.institutionSUNY Downstateen_US
dc.description.departmentDermatologyen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of America


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