Mitochondrial hitch-hiking of Mapt mRNA maintains Tau levels in axons

Abstract

Hitch-hiking of transcripts on organelles, including mitochondria, has emerged as a common pathway to transport mRNAs into the axon to enable their local translation. However, the extent of mitochondrial mRNA association in vivo has not been established. Here we report the landscape of mitochondrial mRNA association in two nerve tissues, the retinal ganglion cell derived optic nerve and the motor neuron derived part of the sciatic nerve. This revealed astonishing tissue diversity between mitochondria associated mRNAs that can partly be explained by the lack of expression of the mitochondrially anchored RNA-binding protein SYNJ2a in motor neurons. This diversity led us to discover that also MAPT mRNA, encoding the axon-enriched microtubule associated protein Tau, is transported via the mitochondrial RNA anchoring complex SYNJ2a/SYNJ2BP into axons of glutamatergic neurons. Loss of SYNJ2BP prevents axonal localization of MAPT and miss-sorting of Tau, consequently stunting axonal growth in cultured hippocampal neurons. This connects mitochondrial transport to the maintenance of the local cytoskeleton and axonal growth in glutamatergic neurons.