Miniatura

Fitxers

872355.pdf (50.52 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2025-01-09

Tots els drets reservats

Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/220250

Mis-splicing of a neuronal microexon promotes CPEB4 aggregation in ASD

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1038/s41586-024-08289-w

Resum

The inclusion of microexons by alternative splicing occurs frequently in neuronal proteins. The roles of these sequences are largely unknown, and changes in their degree of inclusion are associated with neurodevelopmental disorders1. We have previously shown that decreased inclusion of a 24-nucleotide neuron-specific microexon in CPEB4, a RNA-binding protein that regulates translation through cytoplasmic changes in poly(A) tail length, is linked to idiopathic autism spectrum disorder (ASD)2. Why this microexon is required and how small changes in its degree of inclusion have a dominant-negative effect on the expression of ASD-linked genes is unclear. Here we show that neuronal CPEB4 forms condensates that dissolve after depolarization, a transition associated with a switch from translational repression to activation. Heterotypic interactions between the microexon and a cluster of histidine residues prevent the irreversible aggregation of CPEB4 by competing with homotypic interactions between histidine clusters. We conclude that the microexon is required in neuronal CPEB4 to preserve the reversible regulation of CPEB4-mediated gene expression in response to neuronal stimulation.

Matèries

Trastorns de l'espectre autista, Nucleòtids, Neurones

Matèries (anglès)

Autism spectrum disorders, Nucleotides, Neurons

Citació

Col·leccions

Articles publicats en revistes (Física Aplicada)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

GARCIA CABAU, Carla, BARTOMEU, Anna, TESEI, Giulio, CHIT CHEUNG, Kai, POSE UTRILLA, Julia, PICÓ, Sara, BALACEANU, Andreea, DURAN-ARQUÉ, Berta, FERNÁNDEZ-ALFARA, Marcos, MARTÍN, Judit, DE PACE, Cesare, RUIZ-PEREZ, Lorena, GARCÍA ARROYO, Jesús, BATTAGLIA, Giuseppe, LUCAS, J. josé, HERVÁS, Rubén, LINDORFF-LARSEN, Kresten, MÉNDEZ, Raúl, SALVATELLA I GIRALT, Xavier. Mis-splicing of a neuronal microexon promotes CPEB4 aggregation in ASD. _Nature_. 2025. Vol. 637, núm. 496-503. [consulta: 23 de gener de 2026]. ISSN: 0028-0836. [Disponible a: https://hdl.handle.net/2445/220250]

Exportar metadades

JSON - METS

Compartir registre