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Mol Biol Cell. 2016 Feb 1;27(3):518-34. doi: 10.1091/mbc.E15-07-0504. Epub 2015 Dec 10.

hnRNP-Q1 represses nascent axon growth in cortical neurons by inhibiting Gap-43 mRNA translation.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
2
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282.
3
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.
4
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322 gbassel@emory.edu.

Abstract

Posttranscriptional regulation of gene expression by mRNA-binding proteins is critical for neuronal development and function. hnRNP-Q1 is an mRNA-binding protein that regulates mRNA processing events, including translational repression. hnRNP-Q1 is highly expressed in brain tissue, suggesting a function in regulating genes critical for neuronal development. In this study, we have identified Growth-associated protein 43 (Gap-43) mRNA as a novel target of hnRNP-Q1 and have demonstrated that hnRNP-Q1 represses Gap-43 mRNA translation and consequently GAP-43 function. GAP-43 is a neuronal protein that regulates actin dynamics in growth cones and facilitates axonal growth. Previous studies have identified factors that regulate Gap-43 mRNA stability and localization, but it remains unclear whether Gap-43 mRNA translation is also regulated. Our results reveal that hnRNP-Q1 knockdown increased nascent axon length, total neurite length, and neurite number in mouse embryonic cortical neurons and enhanced Neuro2a cell process extension; these phenotypes were rescued by GAP-43 knockdown. Additionally, we have identified a G-quadruplex structure in the 5' untranslated region of Gap-43 mRNA that directly interacts with hnRNP-Q1 as a means to inhibit Gap-43 mRNA translation. Therefore hnRNP-Q1-mediated repression of Gap-43 mRNA translation provides an additional mechanism for regulating GAP-43 expression and function and may be critical for neuronal development.

PMID:
26658614
PMCID:
PMC4751602
DOI:
10.1091/mbc.E15-07-0504
[Indexed for MEDLINE]
Free PMC Article

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