RNA localization is a key determinant of neurite-enriched proteome

被引:137
作者
Zappulo, Alessandra [1 ]
van den Bruck, David [1 ]
Mattioli, Camilla Ciolli [1 ]
Franke, Vedran [2 ]
Imami, Koshi [3 ]
McShane, Erik [3 ]
Moreno-Estelles, Mireia [4 ]
Calviello, Lorenzo [5 ]
Filipchyk, Andrei [6 ]
Peguero-Sanchez, Esteban [1 ,7 ]
Mueller, Thomas [8 ]
Woehler, Andrew [9 ]
Birchmeier, Carmen [8 ]
Merino, Enrique [7 ]
Rajewsky, Nikolaus [6 ]
Ohler, Uwe [5 ]
Mazzoni, Esteban O. [4 ]
Selbach, Matthias [3 ]
Akalin, Altuna [2 ]
Chekulaeva, Marina [1 ]
机构
[1] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Noncoding RNAs & Mech Cytoplasm Gene Regulat, D-13125 Berlin, Germany
[2] Max Delbruck Ctr Mol Med, BIMSB Bioinformat Platform, D-13125 Berlin, Germany
[3] Max Delbruck Ctr Mol Med, Proteome Dynam, D-13125 Berlin, Germany
[4] NYU, Dept Biol, New York, NY 10003 USA
[5] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Computat Regulatory Genom, D-13125 Berlin, Germany
[6] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Syst Biol Gene Regulatory Elements, D-13125 Berlin, Germany
[7] UNAM, Dept Microbiol Mol, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
[8] Max Delbruck Ctr Mol Med, Dev Biol Signal Transduct, D-13125 Berlin, Germany
[9] Max Delbruck Ctr Mol Med, BIMSB Light Microscopy Platform, D-13125 Berlin, Germany
关键词
EMBRYONIC STEM-CELLS; MESSENGER-RNA; BINDING PROTEINS; LOCAL TRANSLATION; GLOBAL ANALYSIS; NERVOUS-SYSTEM; CIRCULAR RNAS; 3' UTRS; REVEALS; TRANSCRIPTOME;
D O I
10.1038/s41467-017-00690-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:13
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