This project was led by @sh4nnonmiller and @KatelynMGreen with help from @alanboyle.bsky.social and @BarmadaLab and everyone in @realtoddlab.bsky.social Thanks to NIH and VAResearch for support! 5/5

Knowing the template for DPR production from RAN translation in C9orf72 FTD and ALS is a key first step to developing effective therapies for these currently untreatable conditions. 4/5

In contrast, we find no evidence for lariat RNAs or intron retention as endogenous templates for RAN translation, as both species are very rare and inefficient translation templates in neurons. 3/5

We used nanopore coupled to 5'RACE to find the 5' end of repeat containing RNAs. 95%+ of repeat RNAs initiate in the intron rather than at annotated start sites. These short (~80nt) 5' leader mRNAs are capped and polyadenylated and robustly translated in reporter assays. 2/5