RBNAGE · Deciphering the role of RNA biological noise in aging using long-reads transcriptomics.

The ultimate goal of this proposal is to decipher the role of the RNA biological noise (RBN) in the ageing brain. RBN represents a rare but real pool of RNA molecules generated as a result of transcriptional instability. However, as the RBN can only be extracted by full-length single-molecule transcript sequencing, whether RBN is associated with decline processes such as aging and neurodegeneration, remains to be elucidated. To evaluate this association, I will use readily-available data, including long-reads, single cell and spatial transcriptomics of aging mice brains. First, I will develop a methodology to distinguish technical noise from RBN in long-reads transcriptomics. Second, I will characterize the RBN to decipher its contribution to aging. Third, I will study the cell-type-specific and brain-region-specific RBN. To carry out this project, I will work with Dr. Conesa, expert in long-reads transcriptomics, method development and multi-omics. This timely work will benefit from collaboration with world leaders in single-molecule technologies participating in MSCA-DN 2021 “LongTREC” to study transcriptome biology under the coordination of Dr. Conesa. Successful completion of this project will contribute insights and software to understand the RBN across the single-molecule transcriptome, not only in the context of aging and neurobiology but also for researchers to use in other biological contexts. This project could also set important first steps towards better health, healthy aging, and a decrease in avoidable neurodegeneration.