RNA ligation in neurons by RtcB inhibits axon regeneration

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-07, Vol.112 (27), p.8451-8456
Main Authors: Kosmaczewski, Sara Guckian, Sung Min Han, Bingjie Han, Benjamin Irving Meyer, Huma S. Baig, Wardah Athar, Alexander T. Lin-Moore, Michael R. Koelle, Marc Hammarlund
Format: Article
Language:English
Subjects:
Amino Acyl-tRNA Synthetases - genetics
Amino Acyl-tRNA Synthetases - metabolism
Animals
Animals, Genetically Modified
axon regeneration
Axons - metabolism
Axons - physiology
Axotomy - methods
Biological Sciences
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
introns
Luminescent Proteins - genetics
Luminescent Proteins - metabolism
messenger RNA
Microscopy, Fluorescence
Mutation
Nerve Regeneration
nerve tissue
Neurons
Neurons - metabolism
Neurons - physiology
Proteins
RNA ligase (ATP)
RNA Ligase (ATP) - genetics
RNA Ligase (ATP) - metabolism
RNA ligation
RNA, Helminth - genetics
RNA, Helminth - metabolism
RNA, Transfer - genetics
RNA, Transfer - metabolism
RtcB
Transfer RNA
unfolded protein response
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1502948112