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Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian Nervous System.

Neuron | 2018

N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping further reveals a dynamic m6A landscape in the adult DRG upon injury. Loss of either m6A methyltransferase complex component Mettl14 or m6A-binding protein Ythdf1 globally attenuates injury-induced protein translation in adult DRGs and reduces functional axon regeneration in the peripheral nervous system in vivo. Furthermore, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult central nervous system is attenuated upon Mettl14 knockdown. Our study reveals a critical epitranscriptomic mechanism in promoting injury-induced protein synthesis and axon regeneration in the adult mammalian nervous system.

Pubmed ID: 29346752 RIS Download

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: RM1 HG008935
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007445
  • Agency: NINDS NIH HHS, United States
    Id: R37 NS047344
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA043361
  • Agency: NINDS NIH HHS, United States
    Id: P01 NS097206
  • Agency: NINDS NIH HHS, United States
    Id: R35 NS097370

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This is a list of tools and resources that we have found mentioned in this publication.


SAM format (tool)

RRID:SCR_012093

A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.

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Synaptic Systems (tool)

RRID:SCR_013612

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STAR (tool)

RRID:SCR_015899

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

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STAR (tool)

RRID:SCR_004463

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

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goat anti-rabbit IgG-HRP (antibody)

RRID:AB_631746

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goat anti-mouse IgG-HRP (antibody)

RRID:AB_631737

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Anti-Gl Syn Antibody (E-4) (antibody)

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Purified anti-Tubulin beta 3 (TUBB3) (antibody)

RRID:AB_10063408

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Phospho-S6 Ribosomal Protein (Ser235/236) (D57.2.2E) XP Rabbit mAb (antibody)

RRID:AB_916156

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YTHDF1 antibody (antibody)

RRID:AB_2217473

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Anti-GAPDH (antibody)

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STMN2 Antibody (antibody)

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ATF-3 (C-19) (antibody)

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RRID:AB_2566826

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BEDTools (software resource)

RRID:SCR_006646

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SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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Trimmomatic (data processing software)

RRID:SCR_011848

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Systems Transcriptional Activity Reconstruction (data or information resource)

RRID:SCR_005622

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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NeuronJ: An ImageJ Plugin for Neurite Tracing and Quantification (data processing software)

RRID:SCR_002074

NeuronJ is an ImageJ plugin to facilitate the tracing and quantification of elongated structures in two-dimensional (2D) images (8-bit gray-scale and indexed color), in particular neurites in fluorescence microscopy images. Sponsors: The development of NeuronJ started while the primary developer ( Dr. Erik Meijering, PhD) was with the Biomedical Imaging Group (collaborating with people from the Laboratory of Cellular Neurobiology) of the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland, and was finished while Dr. Meijering was with the Biomedical Imaging Group Rotterdam in the Netherlands.

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