mRNAs Co-transport with Mitochondria in Neuronal Cells: Sequence Elements and Protein Factors
Neurons are polarized cells with high energetic demands, which are highly dependent on localized translation of nuclear-encoded mRNAs. Yet, the transport mechanisms of the translation machinery components, namely the mRNA, are largely unknown. We showed that mRNAs of nuclear-encoded mitochondrial genes are associated with mitochondria, in both mouse neural-like cell lines and primary neurons. Furthermore, live-imaging of mRNAs, revealed that one of these mRNAs, Cox7c, is not only associated but also co-transported with moving mitochondria along neurites. Interestingly, the Cox7c mRNA coding sequence, and specifically the predicted mitochondrial targeting sequence (MTS), rather than its 3’untranslated region, was the significant domain for the mechanism. Our results suggest that mRNAs encoding mitochondrial proteins are associated and transported with mitochondria in a manner that might involve translation. Genome-wide analysis of mitochondria-associated mRNAs revealed diverse groups of mRNAs, implying a broad phenomenon. To identify the mediators of this association we performed a proteomic identification of mRNA-associated proteins and investigated key candidate’s role in the co-transport. Together, the results support the idea that mitochondria can serve as mRNA shuttles and help regulate the distribution of mRNAs in specific locations within neurons.
