RNA localization is a key determinant of neurite-enriched proteome

• DOI: 10.1038/s41467-017-00690-6
• Publication Date: 2017-09-13T10:04:33Z
• Authors: Alessandra Zappulo; David van den Bruck; Camilla Ciolli Ma...; Vedran Franke; Koshi Imami; Erik McShane; Mireia Moreno-Est...; Lorenzo Calviello; Andrei Filipchyk; Esteban Peguero-S...; Thomas Müller; Andrew Woehler; Carmen Birchmeier; Enrique Merino; Nikolaus Rajewsky; Uwe Ohler; Esteban O. Mazzoni; Matthias Selbach; Altuna Akalin; Marina Chekulaeva
• Keywords: Neurons; 0301 basic medicine; Cancer Research; RNA, Untranslated; Proteome; Science; Stem Cells; Q; Proteins; Cell Differentiation; Article; Mice; Protein Transport; 03 medical and health sciences; Cardiovascular and Metabolic Diseases; Protein Biosynthesis; Neurites; Animals; RNA, Messenger; Technology Platforms; Function and Dysfunction of the Nervous System; Transcriptome; Cells, Cultured

AbstractProtein subcellular localization is fundamental to the establishment of the body axis, cell migration, synaptic plasticity, and a vast range of other biological processes. Protein localization occurs through three mechanisms: protein transport, mRNA localization, and local translation. However, the relative contribution of each process to neuronal polarity remains unknown. Using neurons differentiated from mouse embryonic stem cells, we analyze protein and RNA expression and translation rates in isolated cell bodies and neurites genome-wide. We quantify 7323 proteins and the entire transcriptome, and identify hundreds of neurite-localized proteins and locally translated mRNAs. Our results demonstrate that mRNA localization is the primary mechanism for protein localization in neurites that may account for half of the neurite-localized proteome. Moreover, we identify multiple neurite-targeted non-coding RNAs and RNA-binding proteins with potential regulatory roles. These results provide further insight into the mechanisms underlying the establishment of neuronal polarity.