mRNA stability and m6A are major determinants of subcellular mRNA localization in neurons. Loedige et al.

Original Images to Publication: “mRNA stability and m6A are major determinants of subcellular mRNA localization".
For cells to perform their biological functions, they need to adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model of mRNA localization involves specific sequences called “zipcodes” that direct mRNAs to their proper locations. However, while thousands of mRNAs localize within cells, only a few zipcodes have been identified, suggesting that additional mechanisms contribute to localization. Here we assess the role of mRNA stability in localization by combining isolation of the soma and neurites of primary cortical and mESC-derived neurons, SLAM-seq, m6A-RIP-seq, perturbation of mRNA destabilization mechanisms, and analysis of multiple mRNA localization datasets. We show that depletion of mRNA destabilization elements, such as m6A, AU-rich elements, and suboptimal codons, functions as a mechanism that mediates the localization of mRNAs associated with housekeeping functions to neurites in several types of neurons.