A. Abashidze, Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons. PLoS One, 2014.

S. L. Anderson, Familial Dysautonomia Is Caused by Mutations of the IKAP Gene, The American Journal of Human Genetics, vol.68, issue.3, pp.753-761, 2001.
DOI : 10.1086/318808

S. L. Anderson, Nutraceutical-mediated restoration of wild-type levels of IKBKAP-encoded IKAP protein in familial dysautonomia-derived cells, Molecular Nutrition & Food Research, vol.15, issue.4, 2012.
DOI : 10.1007/s10286-005-0288-1

S. L. Anderson, EGCG corrects aberrant splicing of IKAP mRNA in cells from patients with familial dysautonomia, Biochemical and Biophysical Research Communications, vol.310, issue.2, pp.627-660, 2003.
DOI : 10.1016/j.bbrc.2003.09.019

S. L. Anderson, Tocotrienols induce IKBKAP expression: a possible therapy for familial dysautonomia, Biochemical and Biophysical Research Communications, vol.306, issue.1, pp.303-312, 2003.
DOI : 10.1016/S0006-291X(03)00971-9

S. Arastu-kapur, Nonproteasomal Targets of the Proteasome Inhibitors Bortezomib and Carfilzomib: a Link to Clinical Adverse Events, Clinical Cancer Research, vol.17, issue.9, pp.2734-2777, 2011.
DOI : 10.1158/1078-0432.CCR-10-1950

B. A. Azakir, Proteasome inhibitors increase missense mutated dysferlin in patients with muscular dystrophy, Science Translational Medicine, vol.399, issue.2, pp.250-112, 2014.
DOI : 10.1016/j.ab.2009.12.026

I. Basak, microRNAs as neuroregulators, biomarkers and therapeutic agents in neurodegenerative diseases, Cellular and Molecular Life Sciences, vol.33, issue.Suppl, pp.811-838, 2016.
DOI : 10.1016/j.nbd.2008.11.009

F. Belinky, PathCards: multi-source consolidation of human biological pathways, Database, vol.2015, issue.0, 2015.
DOI : 10.1093/database/bav006
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343183

P. Bellare, A role for ubiquitin in the spliceosome assembly pathway, Nature Structural & Molecular Biology, vol.260, issue.5, pp.444-51, 2008.
DOI : 10.1101/gad.1.9.1014

S. Bieler, Low Dose Proteasome Inhibition Affects Alternative Splicing, Journal of Proteome Research, vol.11, issue.8, pp.3947-54, 2012.
DOI : 10.1021/pr300435c

N. Boone, Genome-wide analysis of familial dysautonomia and kinetin target genes with patient olfactory ecto-mesenchymal stem cells, Human Mutation, vol.1073, issue.1074, pp.530-570, 2012.
DOI : 10.1016/j.brainres.2005.12.059
URL : https://hal.archives-ouvertes.fr/hal-00701177

N. Boone, Olfactory Stem Cells, a New Cellular Model for Studying Molecular Mechanisms Underlying Familial Dysautonomia, PLoS ONE, vol.5, issue.1074, 2010.
DOI : 10.1371/journal.pone.0015590.s003
URL : http://doi.org/10.1371/journal.pone.0015590

M. Chaverra, The Familial Dysautonomia disease gene, Ikbkap/Elp1, is required in the developing and adult central nervous system, Dis. Model Mech, 2017.

D. Cheishvili, IKAP/Elp1 involvement in cytoskeleton regulation and implication for familial dysautonomia, Human Molecular Genetics, vol.20, issue.8, pp.1585-94, 2011.
DOI : 10.1093/hmg/ddr036

D. Cheishvili, Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study, Journal of Molecular Neuroscience, vol.40, issue.4, pp.382-91, 2016.
DOI : 10.1021/bi00091a020

D. Cheishvili, IKAP/hELP1 deficiency in the cerebrum of familial dysautonomia patients results in down regulation of genes involved in oligodendrocyte differentiation and in myelination, Human Molecular Genetics, vol.16, issue.17, pp.2097-104, 2007.
DOI : 10.1093/hmg/ddm157

D. Chen, EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment, Adv. Clin. Chem, vol.53, pp.155-77, 2011.
DOI : 10.1016/B978-0-12-385855-9.00007-2
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304302/pdf

C. H. Chou, miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database, Nucleic Acids Research, vol.44, issue.D1, pp.239-286, 2016.
DOI : 10.1093/nar/gkv1258
URL : http://doi.org/10.1093/nar/gkv1258

I. Chumakov, Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy, Orphanet Journal of Rare Diseases, vol.32, issue.1, p.201, 2014.
DOI : 10.1186/s13023-014-0199-0

P. Close, Transcription Impairment and Cell Migration Defects in Elongator-Depleted Cells: Implication for Familial Dysautonomia, Molecular Cell, vol.22, issue.4, pp.521-552, 2006.
DOI : 10.1016/j.molcel.2006.04.017
URL : http://doi.org/10.1016/j.molcel.2006.04.017

R. Cohen-kupiec, Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia, PLoS ONE, vol.57, issue.4, 2011.
DOI : 10.1371/journal.pone.0019147.s005

I. Cornez, Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells, Biochemical Pharmacology, vol.75, issue.11, 2008.
DOI : 10.1016/j.bcp.2008.03.006

C. Creppe and M. Buschbeck, Elongator: An Ancestral Complex Driving Transcription and Migration through Protein Acetylation, Journal of Biomedicine and Biotechnology, vol.11, issue.2, p.924898, 2011.
DOI : 10.1038/47412
URL : http://doi.org/10.1155/2011/924898

C. Creppe, Elongator Controls the Migration and Differentiation of Cortical Neurons through Acetylation of ??-Tubulin, Cell, vol.136, issue.3, pp.551-64, 2009.
DOI : 10.1016/j.cell.2008.11.043

M. P. Cuajungco, Tissue-Specific Reduction in Splicing Efficiency of IKBKAP Due to the Major Mutation Associated with Familial Dysautonomia, The American Journal of Human Genetics, vol.72, issue.3, pp.749-58, 2003.
DOI : 10.1086/368263

F. J. Dennissen, The ubiquitin proteasome system in neurodegenerative diseases: Culprit, accomplice or victim?, Progress in Neurobiology, vol.96, issue.2, pp.190-207, 2012.
DOI : 10.1016/j.pneurobio.2012.01.003

H. Dweep and N. Gretz, miRWalk2.0: a comprehensive atlas of microRNA-target interactions, Nature Methods, vol.12, issue.8, p.697
DOI : 10.1186/1471-2164-11-224

H. Y. Fu, Overexpression of endoplasmic reticulum-resident chaperone attenuates cardiomyocyte death induced by proteasome inhibition, Cardiovascular Research, vol.79, issue.4, pp.600-610, 2008.
DOI : 10.1093/cvr/cvn128

S. Glatt and C. W. Muller, Structural insights into Elongator function, Current Opinion in Structural Biology, vol.23, issue.2, pp.235-277, 2013.
DOI : 10.1016/j.sbi.2013.02.009

N. A. Hawkes, Purification and Characterization of the Human Elongator Complex, Journal of Biological Chemistry, vol.268, issue.4, pp.3047-52, 2002.
DOI : 10.1093/nar/22.22.4673

M. Hervé and E. C. Ibrahim, MicroRNA screening identifies a link between NOVA1 expression and a low level of IKAP in familial dysautonomia, Disease Models & Mechanisms, vol.9, issue.8, pp.899-909, 2016.
DOI : 10.1242/dmm.025841

B. J. Hunnicutt, IKAP/Elp1 Is Required In Vivo for Neurogenesis and Neuronal Survival, but Not for Neural Crest Migration, PLoS ONE, vol.20, issue.1, 2012.
DOI : 10.1371/journal.pone.0032050.g007

M. Z. Jackson, A neuron autonomous role for the familial dysautonomia gene ELP1 in sympathetic and sensory target tissue innervation, Development, vol.141, issue.12, pp.2452-61, 2014.
DOI : 10.1242/dev.107797

G. S. Kaplan, Proteasome inhibitors in cancer therapy: Treatment regimen and peripheral neuropathy as a side effect, Free Radical Biology and Medicine, vol.103, pp.1-13, 2016.
DOI : 10.1016/j.freeradbiomed.2016.12.007

T. Karlsborn, Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes, RNA Biology, vol.69, issue.12, pp.1519-1547, 2014.
DOI : 10.1038/ncomms1173

R. W. King, How Proteolysis Drives the Cell Cycle, Science, vol.274, issue.5293, pp.1652-1661, 1996.
DOI : 10.1126/science.274.5293.1652

A. F. Kisselev, Proteasome Inhibitors: An Expanding Army Attacking a Unique Target, Chemistry & Biology, vol.19, issue.1, pp.99-115, 2012.
DOI : 10.1016/j.chembiol.2012.01.003
URL : http://doi.org/10.1016/j.chembiol.2012.01.003

S. Komili and P. A. Silver, Coupling and coordination in gene expression processes: a systems biology view, Nature Reviews Genetics, vol.14, issue.1, pp.38-48, 2008.
DOI : 10.1038/msb4100106

G. A. Koumbadinga, Increased stability of heterogeneous ribonucleoproteins by a deacetylase inhibitor, Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, vol.1849, issue.8, pp.1095-103, 2015.
DOI : 10.1016/j.bbagrm.2015.05.001

S. E. Kurtin and E. Bilotti, Novel agents for the treatment of multiple myeloma: proteasome inhibitors and immunomodulatory agents, J. Adv. Pract. Oncol, vol.4, pp.307-328, 2013.

S. Laguesse, A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis, Developmental Cell, vol.35, issue.5, pp.553-67, 2015.
DOI : 10.1016/j.devcel.2015.11.005

B. Lamothe, Proteasome inhibitor carfilzomib complements ibrutinib's action in chronic lymphocytic leukemia, Blood, vol.125, issue.2, pp.407-417, 2015.
DOI : 10.1182/blood-2014-07-585364
URL : http://www.bloodjournal.org/content/bloodjournal/125/2/407.full.pdf

V. R. Moulton, Ubiquitination Regulates Expression of the Serine/Arginine-rich Splicing Factor 1 (SRSF1) in Normal and Systemic Lupus Erythematosus (SLE) T Cells, Journal of Biological Chemistry, vol.181, issue.7, 2014.
DOI : 10.1084/jem.184.4.1313

E. Muchtar, A practical review on carfilzomib in multiple myeloma, European Journal of Haematology, vol.34, issue.6, pp.564-77, 2016.
DOI : 10.1200/JCO.2013.49.6166

S. Naftelberg, Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia, PLOS Genetics, vol.73, issue.12, 2016.
DOI : 10.1371/journal.pgen.1006486.s009

L. S. Nguyen, Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology, Molecular Autism, vol.283, issue.14, 2016.
DOI : 10.1074/jbc.M706499200
URL : https://hal.archives-ouvertes.fr/inserm-01252689

L. Norcliffe-kaufmann, Familial dysautonomia: History, genotype, phenotype and translational research, Progress in Neurobiology, vol.152, 2016.
DOI : 10.1016/j.pneurobio.2016.06.003

T. Ravid and M. Hochstrasser, Diversity of degradation signals in the ubiquitin???proteasome system, Nature Reviews Molecular Cell Biology, vol.20, issue.9, pp.679-90, 2008.
DOI : 10.1091/mbc.7.9.1343

M. Sado, Protective effect against Parkinson's disease-related insults through the activation of XBP1, Brain Research, vol.1257, pp.16-24, 2009.
DOI : 10.1016/j.brainres.2008.11.104

D. Sardana, Drug repositioning for orphan diseases, Briefings in Bioinformatics, vol.12, issue.4, pp.346-56, 2011.
DOI : 10.1093/bib/bbr021

G. Schratt, microRNAs at the synapse, Nature Reviews Neuroscience, vol.19, issue.12, pp.842-851, 2009.
DOI : 10.1038/nrn2763

K. Scott, Bortezomib for the treatment of multiple myeloma, Cochrane Database Syst. Rev, vol.4, 2016.

S. A. Slaugenhaupt, Tissue-Specific Expression of a Splicing Mutation in the IKBKAP Gene Causes Familial Dysautonomia, The American Journal of Human Genetics, vol.68, issue.3, pp.598-605, 2001.
DOI : 10.1086/318810

S. A. Slaugenhaupt, Rescue of a human mRNA splicing defect by the plant cytokinin kinetin, Human Molecular Genetics, vol.13, issue.4, pp.429-465, 2004.
DOI : 10.1093/hmg/ddh046

J. Q. Svejstrup, Elongator complex: how many roles does it play?, Current Opinion in Cell Biology, vol.19, issue.3, pp.331-337, 2007.
DOI : 10.1016/j.ceb.2007.04.005

A. S. Tsimokha, DNA damage modulates interactions between microRNAs and the 26S proteasome, Oncotarget, vol.5, issue.11, pp.3555-67, 2014.
DOI : 10.18632/oncotarget.1957
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116502

Y. Ueki, Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia, eNeuro, vol.3, issue.5, 2016.
DOI : 10.1523/ENEURO.0143-16.2016

I. S. Vlachos, DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions, Nucleic Acids Research, vol.43, issue.D1, pp.153-162, 2015.
DOI : 10.1093/nar/gku1215

I. S. Vlachos, DIANA-miRPath v3.0: deciphering microRNA function with experimental support, Nucleic Acids Research, vol.43, issue.W1, pp.460-466, 2015.
DOI : 10.1093/nar/gkv403

M. L. Volvert, MicroRNAs tune cerebral cortical neurogenesis, Cell Death and Differentiation, vol.12, issue.10, pp.1573-81, 2012.
DOI : 10.1016/S0960-9822(02)00809-6
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438503

H. Xu, Dimerization of elongator protein 1 is essential for Elongator complex assembly, Proceedings of the National Academy of Sciences, vol.8, issue.11, pp.10697-702, 2015.
DOI : 10.1128/MCB.8.11.4936

M. Yoshida, Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia, Proceedings of the National Academy of Sciences, vol.2, issue.9, pp.2764-2773, 2015.
DOI : 10.1146/annurev-genet-110410-132531

N. Zeltner, Capturing the biology of disease severity in a PSC-based model of familial dysautonomia, Nature Medicine, vol.87, issue.12, pp.1421-1427, 2016.
DOI : 10.1038/nmeth.2722

X. Zhang, MicroRNA-101 Suppresses Tumor Cell Proliferation by Acting as an Endogenous Proteasome Inhibitor via Targeting the Proteasome Assembly Factor POMP, Molecular Cell, vol.59, issue.2, pp.243-57, 2015.
DOI : 10.1016/j.molcel.2015.05.036

A. C. Contributions-e, designed and obtained funding for the study. M.H. and E.C.I performed the experiments, I. analyzed the data and wrote the manuscript