RNA localization is a key determinant of neurite-enriched proteome

Alessandra Zappulo, David Bruck, Camilla Ciolli Mattioli, Vedran Franke, Koshi Imami, Erik McShane, Mireia Moreno-Estelles, Lorenzo Calviello, Andrei Filipchyk, Esteban Peguero-Sanchez, Thomas Müller, Andrew Woehler, Carmen Birchmeier, Enrique Merino, Nikolaus Rajewsky, Uwe Ohler, Esteban O. Mazzoni, Matthias Selbach, Altuna Akalin and Marina Chekulaeva ()
Additional contact information
Alessandra Zappulo: Max Delbrück Center for Molecular Medicine
David Bruck: Max Delbrück Center for Molecular Medicine
Camilla Ciolli Mattioli: Max Delbrück Center for Molecular Medicine
Vedran Franke: Max Delbrück Center for Molecular Medicine
Koshi Imami: Max Delbrück Center for Molecular Medicine
Erik McShane: Max Delbrück Center for Molecular Medicine
Mireia Moreno-Estelles: New York University
Lorenzo Calviello: Max Delbrück Center for Molecular Medicine
Andrei Filipchyk: Max Delbrück Center for Molecular Medicine
Esteban Peguero-Sanchez: Max Delbrück Center for Molecular Medicine
Thomas Müller: Max Delbrück Center for Molecular Medicine
Andrew Woehler: Max Delbrück Center for Molecular Medicine
Carmen Birchmeier: Max Delbrück Center for Molecular Medicine
Enrique Merino: UNAM, Av. Universidad 2001
Nikolaus Rajewsky: Max Delbrück Center for Molecular Medicine
Uwe Ohler: Max Delbrück Center for Molecular Medicine
Esteban O. Mazzoni: New York University
Matthias Selbach: Max Delbrück Center for Molecular Medicine
Altuna Akalin: Max Delbrück Center for Molecular Medicine
Marina Chekulaeva: Max Delbrück Center for Molecular Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Protein 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.

Date: 2017
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DOI: 10.1038/s41467-017-00690-6

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