The Role of SRRM3 Isoforms in Microexon Splicing and Their Implications for Autism

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Our research focuses on understanding how tiny gene segments called microexons influence brain development and function. These microexons are crucial for forming complex neural networks, and their misregulation has been linked to Autism Spectrum Disorder (ASD). We recently identified a new version of a key protein, called SRRM3 Ex15+, which may interfere with the normal inclusion of microexons during brain development. This previously overlooked protein variant appears to act as a negative regulator, potentially affecting brain complexity and contributing to ASD-related vulnerabilities. Our study will explore how this SRRM3 Ex15+ variant works by investigating its interactions within cells and its impact on the molecular processes that control microexon inclusion. We will also assess its effects on brain development using human stem cell models and genetically modified mice. By shedding light on this novel regulatory mechanism, our research could uncover new insights into ASD and identify potential therapeutic targets to improve outcomes for individuals with neurodevelopmental disorders.