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Series GSE241269 Query DataSets for GSE241269
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
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.
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.
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
Submission date Aug 21, 2023
Last update date May 01, 2024
Contact name Ana Maria Aransay
Phone 0034944061325
Organization name CIC bioGUNE
Department Genome Analysis Platform
Street address Parque tecnologico de Bizkaia, Building 801-A
City Derio
State/province BIZKAIA
ZIP/Postal code 48160
Country Spain
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7720312 WT_K1
GSM7720313 KO_K2
GSM7720314 KO_L1
BioProject PRJNA1007620

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Supplementary file Size Download File type/resource
GSE241269_RAW.tar 14.3 Mb (http)(custom) TAR (of RESULTS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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