Limited Availability of ZB P1 Restricts Axonal mRNA Localization and Nerve Regeneration Capacity

Document Type

Article

Publication Date

9-2011

Abstract

Subcellular localization of mRNAs is regulated by RNA–protein interactions. Here, we show that introduction of a reporter mRNA with the 3′UTR of β-actin mRNA competes with endogenous mRNAs for binding to ZBP1 in adult sensory neurons. ZBP1 is needed for axonal localization of β-actin mRNA, and introducing GFP with the 3′UTR of β-actin mRNA depletes axons of endogenous β-actin and GAP-43 mRNAs and attenuates both in vitro and in vivo regrowth of severed axons. Consistent with limited levels of ZBP1 protein in adult neurons, mice heterozygous for the ZBP1 gene are haploinsufficient for axonal transport of β-actin and GAP-43 mRNAs and for regeneration of peripheral nerve. Exogenous ZBP1 can rescue the RNA transport deficits, but the axonal growth deficit is only rescued if the transported mRNAs are locally translated. These data support a direct role for ZBP1 in transport and translation of mRNA cargos in axonal regeneration in vitro and in vivo.

Publication Title

EMBO Journal

Volume

30

Issue

22

First Page

4665

Last Page

4677

PubMed ID

21964071

Comments

This article was published in the EMBO Journal, Volume 30, Issue 22, September 2011, Pages 4665-4677.

The published version is available at http://dx.doi.org/10.1038/emboj.2011.347

Copyright © 2011 European Molecular Biology Organization

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