Sudmant, a new professor at Berkeley, is interested broadly on the genomics of aging, but focused today on post-transcriptional gene regulation. The problem that motivated him is selective neuronal vulnerability: As we age, we are more likely to get neurodegenerative diseases, but for unknown reasons these disorders target specific cell types within the brain. Could post-transcriptional phenomena explain this selectivity?
In particular, he focused on the striatum (which is affected in Parkinson’s disease), using a technique known as translating ribosome affinity purification (TRAP) to identify differences in RNA metabolism in D1 and D2 dopaminergic neurons. Surprisingly, he found that D1 neurons specifically accumulated isolated 3’ untranslated regions (UTRs), the non-coding termini of mRNAs.
Why the selectivity? Are D1 neurons special in some way? Indeed, oxygen radicals and certain kinds of age-related markers like lipofuscin accumulate more rapidly in these cells. Sudmant proposes that under aging or related stresses, ribosomes stall on mRNAs, and the unique environment within D1 cells causes the 3’UTRs to be cleaved off.
The 3’UTRs end up getting translated into peptides, potentially contributing to age-related decline in tissue function.
Pioneer: Peter Sudmant (Assistant Professor/Berkeley)
Agent: Chris Patel (Hourglass)