Mbp (myelin basic protein) is the most abundant mRNA in oligodendrocytes MBP functions in compaction, a bizarre cellular phenomenon that extrudes cytoplasm from the myelin sheath. It acts as a molecular glue between adjacent membranes. Hence, it is locally translated. 2/8

We asked which part of the ~1.5-kb Mbp 3' UTR is important for mRNA transport? Ved applied 2 orthogonal techniques to primary olives: - DMS-MaPseq to solve the RNA structure - SLAP-seq - a method he innovated combining ~270 reporters and Boyden chambers cultures 3/8

We found a ~120-nt region sufficient for transport that we call the MLS. Comparing to decades-old results from the Carson lab: - Their RTS regions was not validated. - But our MLS partially overlaps with their RLR region. 4/8

Importantly, the MLS can be used to deliver CDS cargos throughout oligodendrocyte processes. Here, we used EGFP as a reporter cargo. 5/8

Next, we used mass spec to ask what proteins associate with the MLS mRNA region. We found hnRNP-F and proteins involved in translation! Our structure of the MLS also had the canonical hnRNP-F-binding GGG(A) motifs! 6/8

Combined w. work from Jackie Trotter & Doug Fields Labs, we propose a RNA switch model: - During transport, hnRNP-F binds unstructured MLS to inhibit translation. - At the cell periphery, membrane-bound Fyn kinase phosphorylates & releases hnRNP-F to initiate translation. 7/8