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Publication : Regulation of axon regeneration by the RNA repair and splicing pathway.

First Author  Song Y Year  2015
Journal  Nat Neurosci Volume  18
Issue  6 Pages  817-25
PubMed ID  25961792 Mgi Jnum  J:233466
Mgi Id  MGI:5784806 Doi  10.1038/nn.4019
Citation  Song Y, et al. (2015) Regulation of axon regeneration by the RNA repair and splicing pathway. Nat Neurosci 18(6):817-25
abstractText  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.
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