NCM 2022: A brief history of splicing: direct RNA sequencing of mouse brain samples from the RIKEN Aging Project

Alternative splicing of RNA allows for a greater number of RNA isoforms and protein variants to be expressed from the same genome and involved in cell specification during development. However, little is known of how dynamic the expression at the isoform level is within a cell type during the ageing process in humans. The brain is resident to the oldest cells in our body, and therefore provides a history of ageing at the molecular level.
Therefore, we set out to understand this basic principle of isoform expression in mouse brain with ageing. This leveraged samples from the RIKEN Aging Project where both sex, age, and housing (SPF versus germ free environment) are gaining a multi-organ insight into the interplay between aging process and inflammation during life — termed inflammageing. Due to the complexity of splicing in the brain, we will leverage long-read direct RNA nanopore sequencing to overcome current sequencing limitations. We will map the dynamic nature of RNA splicing of brain cell types and states of the brain. We envisage discovering linked isoforms and RNA modifications to the ageing process and age-associated diseases, such as Alzheimer’s disease. Overall, the gene changes during aging differ between animals housed in standard specific pathogen-free housing and those in a germ-free environment.