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Nat Commun. 2017 Sep 19;8(1):583. doi: 10.1038/s41467-017-00690-6.

RNA localization is a key determinant of neurite-enriched proteome.

Author information

1
Non-coding RNAs and Mechanisms of Cytoplasmic Gene Regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
2
BIMSB Bioinformatics Platform, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
3
Proteome Dynamics, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
4
Department of Biology, New York University, New York, NY, 10003-6688, USA.
5
Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
6
Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
7
Departamento de Microbiología Molecular, Instituto de Biotecnología, UNAM, Av. Universidad 2001, Cuernavaca, Morelos, CP, 62210, Mexico.
8
Developmental Biology/Signal Transduction, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
9
BIMSB Light Microscopy Platform, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
10
Non-coding RNAs and Mechanisms of Cytoplasmic Gene Regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany. marina.chekulaeva@mdc-berlin.de.

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.Subcellular localization of RNAs and proteins is important for polarized cells such as neurons. Here the authors differentiate mouse embryonic stem cells into neurons, and analyze the local transcriptome, proteome, and translated transcriptome in their cell bodies and neurites, providing a unique resource for future studies on neuronal polarity.

PMID:
28928394
PMCID:
PMC5605627
DOI:
10.1038/s41467-017-00690-6
[Indexed for MEDLINE]
Free PMC Article

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