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| Status |
Public on Mar 06, 2024 |
| Title |
Neddylation orchestrates the complex transcriptional and post-transcriptional program that drives axonal myelination |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the post-translation modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a striking absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Importantly, our data indicate that neddylation exerts a global influence on the complex transcriptional and post-transcriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signalling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation.
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| Overall design |
RNA was isolated from 7 days old mice sciatic nerves from WT (n=4) and Nae1 cKO mice (n=4). Total RNA was treated with DNAse I (Invitrogen) for 30 min at 37 ºC. Then the samples were cleaned with Genejet RNA cleanup and Concentration kit (Thermo Scientific) (the columns were eluted with 20-30µl ultra-pure water), and samples processed for RNA sequencing.
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| Contributor(s) |
Ayuso-García P, Sánchez-Rueda A, Velasco-Avilés S, Tamayo-Caro M, Riobello C, Ferrer-Pinos A, Huarte-Sebastian C, Jiménez-Vega S, Buendia I, Cañas-Martin J, Fernández-Susavila H, Guhl R, Laville N, Pérez-Andrés E, Lavín JL, Gonzalez-Lopez M, Cámara NM, Aransay AM, Sutherland JD, Barrio R, Martinez-Chantar ML, Azkargorta M, Elortza F, Soriano-Navarro M, Matute C, Sánchez-Gómez MV, Pérez-Samartín A, Bravo SB, Kurz T, Lama-Díaz T, Blanco MG, Haddad S, Rossor AM, Record CJ, Reilly MM, Varela-Rey M, Woodhoo A, Alvarez V, Aparicio-Rey A, Esquinas-Román EM, Rodríguez Ponte C, Lozano J, Bayón-Cordero L, van Hasselt PM |
| Citation(s) |
38608019 |
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| Submission date |
Aug 21, 2023 |
| Last update date |
May 01, 2024 |
| Contact name |
Ana Maria Aransay |
| E-mail(s) |
amaransay@cicbiogune.es
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| Phone |
0034944061325
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| Organization name |
CIC bioGUNE
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| Department |
Genome Analysis Platform
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| Street address |
Parque tecnologico de Bizkaia, Building 801-A
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| City |
Derio |
| State/province |
BIZKAIA |
| ZIP/Postal code |
48160 |
| Country |
Spain |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1007620 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241269_RAW.tar |
14.3 Mb |
(http)(custom) |
TAR (of RESULTS) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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