Alternative splicing controls pan-neuronal homeobox gene expression.

Autor:	Leyva-Díaz E; Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA; eleyva@umh.es.; Department of Developmental Neurobiology, Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas [CSIC]-Universidad Miguel Hernández [UMH]), 03550 Sant Joan d'Alacant, Spain., Cesar M; Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA., Pe K; Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA., Jordá-Llorens JI; Department of Developmental Neurobiology, Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas [CSIC]-Universidad Miguel Hernández [UMH]), 03550 Sant Joan d'Alacant, Spain., Valdivia J; Department of Developmental Neurobiology, Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas [CSIC]-Universidad Miguel Hernández [UMH]), 03550 Sant Joan d'Alacant, Spain., Hobert O; Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2024 Dec 27. Date of Electronic Publication: 2024 Dec 27.
DOI:	10.1101/gad.352184.124
Abstrakt:	The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of Caenorhabditis elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 ("CASP of nematodes") in C. elegans How gene expression from this complex locus is controlled-and, in C. elegans , directed to all cells of the nervous system-has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75, the C. elegans homolog of vertebrate CELF proteins. During embryogenesis, the cone-1&ceh-44 locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript exclusively in the nervous system. Hence, UNC-75/CELF-mediated alternative splicing not only directs pan-neuronal gene expression but also excludes a phylogenetically deeply conserved golgin from the nervous system, paralleling surprising spatial specificities of another golgin that we describe here as well. Our findings provide novel insights into how all cells in a nervous system acquire pan-neuronal identity features and reveal unanticipated cellular specificities in Golgi apparatus composition. (© 2024 Leyva-Díaz et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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