title: RNA ligation in neurons by RtcB inhibits axon regeneration.
abstract: Activity of the RNA ligase RtcB has only two known functions: tRNA ligation after intron removal and XBP1 mRNA ligation during activation of the unfolded protein response. Here, we show that RtcB acts in neurons to inhibit axon regeneration after nerve injury. This function of RtcB is independent of its basal activities in tRNA ligation and the unfolded protein response. Furthermore, inhibition of axon regeneration is independent of the RtcB cofactor archease. Finally, RtcB is enriched at axon termini after nerve injury. Our data indicate that neurons have co-opted an ancient RNA modification mechanism to regulate specific and dynamic functions and identify neuronal RtcB activity as a critical regulator of neuronal growth potential.
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Sara Guckian
authors.initials: SG
authors.lastname: Kosmaczewski
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Irving Meyer
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Huma S
authors.initials: HS
authors.lastname: Baig
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Wardah
authors.initials: W
authors.lastname: Athar
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Lin-Moore
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Koelle
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510; marc.hammarlund@yale.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Hammarlund
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D019771:Axotomy / Q000379:methods; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011130:RNA Ligase (ATP) / Q000235:genetics / Q000378:metabolism*; D018510:RNA, Helminth / Q000235:genetics / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D008164:Luminescent Proteins; D018510:RNA, Helminth; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases; C000602271:rtcb-1 protein, C elegans; D011130:RNA Ligase (ATP)
keywords: RNA ligation; RtcB; axon regeneration