PTEN controls alternative splicing of autism spectrum disorder-associated transcripts in primary neurons

Purpose: To identify alternative splicing events in primary Pten-/- neurons as a model for autism spectrum disorder (ASD). Methods: RNA isolation from DIV14 control and cre-mediated Pten-/- primary cortical neuronal, glia-depleted cultures. PE RNA-Seq using Illumina4000 system. Identification of alternatively spliced transcripts in Pten-/- cultures using rMATS and iREAD. Results: More than 900 alternative splicing events were identified in Pten-/- neurons. These are largely related to synaptic and gene expression regulatory processes. Importantly, more than 80 additional autism-associated risk genes were affected upon Pten loss. Conclusion: PTEN-ASD seems to display a multifactorial condition rather than a monogenetic disorder. Overall design: Analysis of alternative splicing in Pten-/- compared to wildtype mouse primary cortical neurons using rMATS and iREAD. Two biological replicates for each condition were analysed.