Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt
- Jernej Murn1,2,
- Kathi Zarnack3,4,
- Yawei J. Yang5,6,7,8,9,10,
- Omer Durak11,12,
- Elisabeth A. Murphy5,6,7,8,9,10,
- Sihem Cheloufi13,14,
- Dilenny M. Gonzalez5,6,7,8,9,10,
- Marianna Teplova15,
- Tomaž Curk16,
- Johannes Zuber17,
- Dinshaw J. Patel15,
- Jernej Ule18,
- Nicholas M. Luscombe3,19,20,21,
- Li-Huei Tsai11,12,
- Christopher A. Walsh5,6,7,8,9,10 and
- Yang Shi1,2
- 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2Division of Newborn Medicine, Boston Children’s Hospital, Boston, Massachusetts 02115, USA;
- 3European Molecular Biology Laboratory (EMBL) European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom;
- 4Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany;
- 5Division of Genetics and Genomics,
- 6Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, Massachusetts 02115, USA;
- 7Department of Pediatrics,
- 8Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 9Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA;
- 10Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA;
- 11Picower Institute for Learning and Memory,
- 12Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
- 13Cancer Center,
- 14Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
- 15Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;
- 16Faculty of Computer and Information Science, University of Ljubljana, 1000 Ljubljana, Slovenia;
- 17The Research Institute of Molecular Pathology, Vienna Biocenter, 1030 Vienna, Austria;
- 18Department of Molecular Neuroscience, University College London Institute of Neurology, London WC1N 3BG, United Kingdom;
- 19UCL Genetics Institute, Department of Genetics, Environment, and Evolution, University College London, London WC1E 6BT, United Kingdom;
- 20Cancer Research UK London Research Institute, London WC2A 3LY, United Kingdom;
- 21Okinawa Institute for Science and Technology Graduate University, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan
- Corresponding authors: yang_shi{at}hms.harvard.edu, murn.jernej{at}gmail.com
Abstract
Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mouse embryos disrupts the shape of migrating neurons, while ectopic expression confers neuronal-like morphology to cells of different nonneuronal lineages. We found that Unkempt is a sequence-specific RNA-binding protein and identified its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking. RNA binding is required for Unkempt-induced remodeling of cellular shape and is directly coupled to a reduced production of the encoded proteins. These findings link post-transcriptional regulation of gene expression with cellular shape and have general implications for the development and disease of multicellular organisms.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.258483.115.
- Received January 9, 2015.
- Accepted February 6, 2015.
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