Neuronal proteome remodeling by microexons and their misregulation in autism spectrum disorder
Speaker: Manuel Irimia
Centro de Regulación Genómica (CRG) [Barcelona, Spain]
Host: Mercedes Dosil
Salón de actos del Centro de Investigación del Cáncer
One of the major questions of Biology is how a single genome sequence can generate the thousands of cell types that form an adult organism. An even more difficult question is how complex behaviors in humans and other mammals are encoded by that same single genome sequence. One molecular mechanism that allows expanding the molecular repertoire encoded in our genomes is alternative splicing. This process impacts up to 95% of human multiexonic genes and, at least in some cases, it has remarkable functional roles. One of the most striking examples is a program of neural microexons we have recently described. These are tiny (3-27 nucleotide) exons that display the highest evolutionary conservation and switch-like regulation during neuronal differentiation. Neural microexons modulate the function of interaction domains of proteins involved in neurogenesis and are modulated by neuronal activity. More importantly, microexons are misregulated in the brains of individuals with autism spectrum disorder, and a mouse model mimicking this misregulation shows multiple hallmarks of this disorder. Here, I will discuss some of the current progress in our understanding of the impact of neural microexons in function and dysfunction.