title: Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity.
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.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Donnelly
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Willis
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Chhavy
authors.initials: C
authors.lastname: Tep
authors.forename: Chunsu
authors.initials: C
authors.lastname: Jiang
authors.forename: Soonmoon
authors.initials: S
authors.lastname: Yoo
authors.forename: N Carolyn
authors.initials: NC
authors.lastname: Schanen
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Kirn-Safran
authors.forename: Jan
authors.initials: J
authors.lastname: van Minnen
authors.forename: Arthur
authors.initials: A
authors.lastname: English
authors.forename: Sung Ok
authors.initials: SO
authors.lastname: Yoon
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Twiss
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D001369:Axons / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019922:GAP-43 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D020439:Growth Cones / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology*; D034443:RNA Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D019922:GAP-43 Protein; D006023:Glycoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C402632:Zbp1 protein, mouse; D049452:Green Fluorescent Proteins