Tricks that our cells use to express their genes in the brain, and how aging affects this

Each RNA in our cells is coated by dozens, if not hundreds of RNA-binding proteins. To understand how these proteins act in our cells, we obtain detailed maps of their RNA binding sites. For this purpose, we developed the nucleotide-resolution UV crosslinking and immunoprecipitation (iCLIP) and a related method called hybrid iCLIP (hiCLIP), which identify protein-RNA and RNA-RNA contacts. I will describe how these methods opened a new window into the diverse mechanisms that enable cells to regulate their gene expression. Mutations in genes encoding RNA-binding proteins can cause motor neuron disease, an age-related neurodegenerative disease. We wish to understand how the cause of this disease is linked to the process of aging in human brain. For this purpose, we characterized gene expression across 10 human brain regions from 480 individuals ranging in age from 16 to 106. We found that the fate of each cell type and each brain region is affected by aging, but in different ways. I will discuss the role that protein-RNA complexes play in regulating such changes in cellular fates, and how this could be important for motor neuron disease.