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

ABSTRACT: 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 s

SUBMITTER: Garcia-Cabau C 

PROVIDER: S-EPMC11711090 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature