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A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3 ' untranslated region AU-rich regulatory element
Journal article   Open access   Peer reviewed

A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3 ' untranslated region AU-rich regulatory element

Soonmoon Yoo, Hak H. Kim, Paul Kim, Christopher J. Donnelly, Ashley L. Kalinski, Deepika Vuppalanchi, Michael Park, Seung J. Lee, Tanuja T. Merianda, Nora I. Perrone-Bizzozero, …
Journal of neurochemistry, v 126(6), pp 792-804
Sep 2013
PMID: 23586486
url
https://europepmc.org/articles/pmc3766383View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

Biochemistry & Molecular Biology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
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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Collaboration types
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Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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