Journal article
A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3 ' untranslated region AU-rich regulatory element
Journal of neurochemistry, v 126(6), pp 792-804
Sep 2013
PMID: 23586486
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Localized translation of axonal mRNAs contributes to developmental and regenerative axon growth. Although untranslated regions (UTRs) of many different axonal mRNAs appear to drive their localization, there has been no consensus RNA structure responsible for this localization. We recently showed that limited expression of ZBP1 protein restricts axonal localization of both b-actin and GAP-43 mRNAs. beta-actin 3'UTR has a defined element for interaction with ZBP1, but GAP-43 mRNA shows no homology to this RNA sequence. Here, we show that an AU-rich regulatory element (ARE) in GAP-43's 30UTR is necessary and sufficient for its axonal localization. Axonal GAP-43 mRNA levels increase after in vivo injury, and GAP-43 mRNA shows an increased half-life in regenerating axons. GAP-43 mRNA interacts with both HuD and ZBP1, and HuD and ZBP1 co-immunoprecipitate in an RNA-dependent fashion. Reporter mRNA with the GAP-43 ARE competes with endogenous beta-actin mRNA for axonal localization and decreases axon length and branching similar to the beta-actin 3'UTR competing with endogenous GAP-43 mRNA. Conversely, over-expressing GAP-43 coding sequence with its 3'UTR ARE increases axonal elongation and this effect is lost when just the ARE is deleted from GAP-43's 3'UTR.
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Details
- Title
- A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3 ' untranslated region AU-rich regulatory element
- Creators
- Soonmoon Yoo - Alfred I duPont Hosp Children, Nemours Biomed Res, Wilmington, DC USAHak H. Kim - Alfred I. duPont Hospital for ChildrenPaul Kim - Alfred I. duPont Hospital for ChildrenChristopher J. Donnelly - Univ Delaware, Dept Biol Sci, Newark, DE USAAshley L. Kalinski - Drexel Univ, Dept Biol, Philadelphia, PA 19104 USADeepika Vuppalanchi - University of DelawareMichael Park - Drexel UniversitySeung J. Lee - University of South CarolinaTanuja T. Merianda - Drexel Univ, Dept Biol, Philadelphia, PA 19104 USANora I. Perrone-Bizzozero - University of New MexicoJeffery L. Twiss - University of South Carolina
- Publication Details
- Journal of neurochemistry, v 126(6), pp 792-804
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- P20GM103464 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Dr. Miriam and Sheldon G. Adelson Medical Research Foundation R01NS041596 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 124124 / Craig H. Neilsen Foundation P20GM103464; R01-NS41596; R01-NS30255 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000324025500011
- Scopus ID
- 2-s2.0-84883740694
- Other Identifier
- 991021892010504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences