Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt.

Genes Dev
Authors
Keywords
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.

Year of Publication
2015
Journal
Genes Dev
Volume
29
Issue
5
Pages
501-12
Date Published
2015 Mar 01
ISSN
1549-5477
URL
DOI
10.1101/gad.258483.115
PubMed ID
25737280
PubMed Central ID
PMC4358403
Links
Grant list
R01 NS032457 / NS / NINDS NIH HHS / United States
R01 NS35129 / NS / NINDS NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 CA118487 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
MH096066 / MH / NIMH NIH HHS / United States
R01 NS035129 / NS / NINDS NIH HHS / United States
R01 MH096066 / MH / NIMH NIH HHS / United States
CA118487 / CA / NCI NIH HHS / United States
R01 GM058012 / GM / NIGMS NIH HHS / United States
GM058012 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States
T32GM007753 / GM / NIGMS NIH HHS / United States