Absence of <i>MBP</i> 3’ UTR in Mice Disrupts mRNA Transport, Myelination, and Motor Learning

Myelin sheath maturation requires compaction, a cellular phenomenon mediated by local translation of myelin basic protein (MBP), which acts as a molecular zipper to join adjacent membranes and extrude the cytoplasm. Contrary to decades-old microinjection experiments indicating that <i>Mbp</i> mRNA transport is restricted to microtubules, we now show using smFISH that endogenous <i>Mbp</i> mRNA granules indeed localize along actin. To validate the <i>in vivo</i> necessity of <i>Mbp</i> mRNA transport and its dependence on the 3' UTR (untranslated region), we replaced the endogenous <i>Mbp</i> 3' UTR with polyA tail sequences. Though these mice have decreased <i>Mbp</i> mRNA levels, this alone could not account for their striking phenotypes - hypomyelination, baseline tremors, and motor learning defects. Thus, we cultured oligodendrocytes from these mice and found defects in both <i>Mbp</i> mRNA localization and local translation. These results demonstrate that the 3' UTR of a locally translated structural protein is critical for both developmental and activity-induced myelination.