title: Regulation of axon regeneration by the RNA repair and splicing pathway.
abstract: Mechanisms governing a neuron's regenerative ability are important but not well understood. We identify Rtca (RNA 3'-terminal phosphate cyclase) as an inhibitor of axon regeneration. Removal of Rtca cell-autonomously enhanced axon regrowth in the Drosophila CNS, whereas its overexpression reduced axon regeneration in the periphery. Rtca along with the RNA ligase Rtcb and its catalyst Archease operate in the RNA repair and splicing pathway important for stress-induced mRNA splicing, including that of Xbp1, a cellular stress sensor. Drosophila Rtca and Archease had opposing effects on Xbp1 splicing, and deficiency of Archease or Xbp1 impeded axon regeneration in Drosophila. Moreover, overexpressing mammalian Rtca in cultured rodent neurons reduced axonal complexity in vitro, whereas reducing its function promoted retinal ganglion cell axon regeneration after optic nerve crush in mice. Our study thus links axon regeneration to cellular stress and RNA metabolism, revealing new potential therapeutic targets for treating nervous system trauma.
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Yuanquan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sretavan
authors.affiliation: Brain and Spinal Injury Center, University of California, San Francisco, California, USA.
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Salegio
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Berg
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiong
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Meltzer
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Trong-Tuong
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Brain and Spinal Injury Center, University of California, San Francisco, California, USA.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bresnahan
authors.affiliation: Brain and Spinal Injury Center, University of California, San Francisco, California, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Beattie
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, California, USA.
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D008025:Ligases / Q000502:physiology; D051379:Mice; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000473:pathology; D012313:RNA / Q000502:physiology*; D012326:RNA Splicing / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D012584:Sciatic Nerve / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C517798:Xbp1 protein, Drosophila; D012313:RNA; D008025:Ligases; C037451:RNA 3'-terminal phosphate cyclase