Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling

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dc.contributor.authorBustos F.
dc.contributor.authorSegarra-Fas A.
dc.contributor.authorNardocci G.
dc.contributor.authorCassidy A.
dc.contributor.authorAntico O.
dc.contributor.authorDavidson L.
dc.contributor.authorBrandenburg L.
dc.contributor.authorMacartney T.J.
dc.contributor.authorToth R.
dc.contributor.authorHastie C.J.
dc.contributor.authorMoran J.
dc.contributor.authorGourlay R.
dc.contributor.authorVarghese J.
dc.contributor.authorSoares R.F.
dc.contributor.authorMontecino M.
dc.contributor.authorFindlay G.M.
dc.date.accessioned2021-08-05T21:31:53Z
dc.date.available2021-08-05T21:31:53Z
dc.date.issued2020-12
dc.descriptionIndexación Scopuses
dc.description.abstractBustos et al. show that SRPK splicing factor kinase has acquired a developmental function— phosphorylating the RNF12 E3 ubiquitin ligase to promote degradation of the transcription factor, REX1. This signaling pathway regulates a neurodevelopmental gene expression program and is mutated in patients with neurodevelopmental disorders. © 2020 The AuthorsConserved protein kinases with core cellular functions have been frequently redeployed during metazoan evolution to regulate specialized developmental processes. The Ser/Arg (SR)-rich splicing factor (SRSF) protein kinase (SRPK), which is implicated in splicing regulation, is one such conserved eukaryotic kinase. Surprisingly, we show that SRPK has acquired the capacity to control a neurodevelopmental ubiquitin signaling pathway. In mammalian embryonic stem cells and cultured neurons, SRPK phosphorylates Ser-Arg motifs in RNF12/RLIM, a key developmental E3 ubiquitin ligase that is mutated in an intellectual disability syndrome. Processive phosphorylation by SRPK stimulates RNF12-dependent ubiquitylation of nuclear transcription factor substrates, thereby acting to restrain a neural gene expression program that is aberrantly expressed in intellectual disability. SRPK family genes are also mutated in intellectual disability disorders, and patient-derived SRPK point mutations impair RNF12 phosphorylation. Our data reveal unappreciated functional diversification of SRPK to regulate ubiquitin signaling that ensures correct regulation of neurodevelopmental gene expression. © 2020 The Authorses
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S1534580720307577?via%3Dihub
dc.identifier.citationDevelopmental Cell, Volume 55, Issue 5, Pages 629 - 647.e77 December 2020es
dc.identifier.doi10.1016/j.devcel.2020.09.025
dc.identifier.issn15345807
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/19701
dc.language.isoenes
dc.publisherCell Presses
dc.subjectRNA Splicing Factores
dc.subjectRNA-binding Proteines
dc.subjectAlternative Splicinges
dc.subjectNeurodevelopmentales
dc.subjectUbiquitin signalinges
dc.titleFunctional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signalinges
dc.typeArtículoes
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