A Dynamic Splicing Program Ensures Proper Synaptic Connections in the Developing Cerebellum
| Autor: | Robert J. Weatheritt, Claudio Sette, Gina La Sala, Vanessa Medici, Francesca Romana Rizzo, Valeria Carola, Benjamin J. Blencowe, Marika Guerra, Vittoria Pagliarini, Chiara Naro, Davide Bonvissuto, Donatella Farini, Daniela Marazziti, Diego Centonze, Alessandra Musella, Eleonora Cesari, Chiara Di Pietro |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Sam68 alternative splicing autism cerebellum development neuronal activity personalized medicine social behavior synaptogenesis RNA Splicing Synaptogenesis Biology General Biochemistry Genetics and Molecular Biology Synapse Mice Purkinje Cells 03 medical and health sciences Exon Splicing factor 0302 clinical medicine Cerebellum Animals Premovement neuronal activity lcsh:QH301-705.5 Adaptor Proteins Signal Transducing Mice Knockout Settore BIO/16 - ANATOMIA UMANA Settore BIO/17 Behavior Animal Alternative splicing RNA-Binding Proteins Splicing Factor U2AF Motor coordination Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) Synapses RNA splicing Female RNA Splice Sites Neuroscience 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Cell reports 31 (2020). doi:10.1016/j.celrep.2020.107703 info:cnr-pdr/source/autori:Donatella Farini, Eleonora Cesari, Robert J. Weatheritt, Gina La Sala, Chiara Naro, Vittoria Pagliarini, Davide Bonvissuto, Vanessa Medici, Marika Guerra, Chiara Di Pietro, Francesca Romana Rizzo, Alessandra Musella, Valeria Carola, Diego Centonze, Benjamin J. Blencowe, Daniela Marazziti, Claudio Sette./titolo:A Dynamic Splicing Program Ensures Proper Synaptic Connections in the Developing Cerebellum/doi:10.1016%2Fj.celrep.2020.107703/rivista:Cell reports/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:31 Cell Reports, Vol 31, Iss 9, Pp-(2020) |
| DOI: | 10.1016/j.celrep.2020.107703 |
| Popis: | Summary Tight coordination of gene expression in the developing cerebellum is crucial for establishment of neuronal circuits governing motor and cognitive function. However, transcriptional changes alone do not explain all of the switches underlying neuronal differentiation. Here we unveiled a widespread and highly dynamic splicing program that affects synaptic genes in cerebellar neurons. The motifs enriched in modulated exons implicated the splicing factor Sam68 as a regulator of this program. Sam68 controls splicing of exons with weak branchpoints by directly binding near the 3′ splice site and competing with U2AF recruitment. Ablation of Sam68 disrupts splicing regulation of synaptic genes associated with neurodevelopmental diseases and impairs synaptic connections and firing of Purkinje cells, resulting in motor coordination defects, ataxia, and abnormal social behavior. These findings uncover an unexpectedly dynamic splicing regulatory network that shapes the synapse in early life and establishes motor and cognitive circuitry in the developing cerebellum. |
| Databáze: | OpenAIRE |
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