Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
Abstract
:1. HuD Functions in Neuronal Development, Synaptic Plasticity and Regeneration
2. HuD Structure and Functioning Mechanisms
3. Possible Roles of HuD in Nervous System Diseases
3.1. Parkinson’s Disease (PD)
3.2. Alzheimer’s Disease (AD)
3.3. Amyotrophic Lateral Sclerosis (ALS)
4. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Bronicki, L.M.; Jasmin, B.J. Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction. RNA 2013, 19, 1019–1037. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abdelmohsen, K.; Hutchison, E.R.; Lee, E.K.; Kuwano, Y.; Kim, M.M.; Masuda, K.; Srikantan, S.; Subaran, S.S.; Marasa, B.S.; Mattson, M.P.; et al. miR-375 inhibits differentiation of neurites by lowering HuD levels. Mol. Cell Biol. 2010, 30, 4197–4210. [Google Scholar] [CrossRef] [Green Version]
- Deschenes-Furry, J.; Perrone-Bizzozero, N.; Jasmin, B.J. The RNA-binding protein HuD: A regulator of neuronal differentiation, maintenance and plasticity. Bioessays 2006, 28, 822–833. [Google Scholar] [CrossRef] [PubMed]
- Akamatsu, W.; Fujihara, H.; Mitsuhashi, T.; Yano, M.; Shibata, S.; Hayakawa, Y.; Okano, H.J.; Sakakibara, S.-I.; Takano, H.; Takano, T.; et al. The RNA-binding protein HuD regulates neuronal cell identity and maturation. Proc. Natl. Acad. Sci. USA 2005, 102, 4625–4630. [Google Scholar] [CrossRef] [Green Version]
- Aranda-Abreu, G.E.; Behar, L.; Chung, S.; Furneaux, H.; Ginzburg, I. Embryonic lethal abnormal vision-like RNA-binding proteins regulate neurite outgrowth and tau expression in PC12 cells. J. Neurosci. 1999, 19, 6907–6917. [Google Scholar] [CrossRef] [PubMed]
- Anderson, K.D.; Sengupta, J.; Morin, M.; Neve, R.L.; Valenzuela, C.F.; Perrone-Bizzozero, N.I. Overexpression of HuD accelerates neurite outgrowth and increases GAP-43 mRNA expression in cortical neurons and retinoic acid-induced embryonic stem cells in vitro. Exp. Neurol. 2001, 168, 250–258. [Google Scholar] [CrossRef] [PubMed]
- Perrone-Bizzozero, N.I.; Tanner, D.C.; Mounce, J.; Bolognani, F. Increased expression of axogenesis-related genes and mossy fibre length in dentate granule cells from adult HuD overexpressor mice. ASN Neuro 2011, 3, 259–270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mobarak, C.D.; Anderson, K.D.; Morin, M.; Beckel-Mitchener, A.; Rogers, S.L.; Furneaux, H.; King, P.; Perrone-Bizzozero, N.I. The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells. Mol. Biol. Cell 2000, 11, 3191–3203. [Google Scholar] [CrossRef] [Green Version]
- Akten, B.; Kye, M.J.; Hao, L.T.; Wertz, M.H.; Singh, S.; Nie, D.; Huang, J.; Merianda, T.T.; Twiss, J.L.; Beattie, C.E.; et al. Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits. Proc. Natl. Acad. Sci. USA 2011, 108, 10337–10342. [Google Scholar] [CrossRef] [Green Version]
- Deschenes-Furry, J.; Belanger, G.; Perrone-Bizzozero, N.; Jasmin, B.J. Post-transcriptional regulation of acetylcholinesterase mRNAs in nerve growth factor-treated PC12 cells by the RNA-binding protein HuD. J. Biol. Chem. 2003, 278, 5710–5717. [Google Scholar] [CrossRef]
- Kasashima, K.; Terashima, K.; Yamamoto, K.; Sakashita, E.; Sakamoto, H. Cytoplasmic localization is required for the mammalian ELAV-like protein HuD to induce neuronal differentiation. Genes Cells 1999, 4, 667–683. [Google Scholar] [CrossRef] [PubMed]
- Pascale, A.; Gusev, P.A.; Amadio, M.; Dottorini, T.; Govoni, S.; Alkon, D.L.; Quattrone, A. Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc. Natl. Acad. Sci. USA 2004, 101, 1217–1222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoo, S.; Kim, H.H.; Kim, P.; Donnelly, C.J.; Kalinski, A.L.; Vuppalanchi, D.; Park, M.; Lee, S.J.; Merianda, T.T.; Perrone-Bizzozero, N.I.; et al. A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3’ untranslated region AU-rich regulatory element. J. Neurochem. 2013, 126, 792–804. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gomes, C.; Lee, S.J.; Gardiner, A.S.; Smith, T.; Sahoo, P.K.; Patel, P.; Thames, E.; Rodriguez, R.; Taylor, R.; Yoo, S.; et al. Axonal localization of neuritin/CPG15 mRNA is limited by competition for HuD binding. J. Cell Sci. 2017, 130, 3650–3662. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Javaherian, A.; Cline, H.T. Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo. Neuron 2005, 45, 505–512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jung, M.; Lee, E.K. RNA-Binding Protein HuD as a Versatile Factor in Neuronal and Non-Neuronal Systems. Biology 2021, 10, 361. [Google Scholar] [CrossRef] [PubMed]
- Perrone-Bizzozero, N.; Bird, C.W. Role of HuD in nervous system function and pathology. Front. Biosci. 2013, 5, 554–563. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hayashi, S.; Yano, M.; Igarashi, M.; Okano, H.J.; Okano, H. Alternative role of HuD splicing variants in neuronal differentiation. J. Neurosci. Res. 2015, 93, 399–409. [Google Scholar] [CrossRef] [PubMed]
- Saito, K.; Fujiwara, T.; Katahira, J.; Inoue, K.; Sakamoto, H. TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD. Biochem. Biophys. Res. Commun. 2004, 321, 291–297. [Google Scholar] [CrossRef]
- Zhu, H.; Hasman, R.A.; Barron, V.A.; Luo, G.; Lou, H. A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators. Mol. Biol. Cell 2006, 17, 5105–5114. [Google Scholar] [CrossRef]
- Zimmerman, A.J.; Hafez, A.K.; Amoah, S.K.; Rodriguez, B.A.; Dell’Orco, M.; Lozano, E.; Hartley, B.J.; Alural, B.; Lalonde, J.; Chander, P.; et al. A psychiatric disease-related circular RNA controls synaptic gene expression and cognition. Mol. Psychiatry 2020, 25, 2712–2727. [Google Scholar] [CrossRef] [Green Version]
- Dell’Orco, M.; Oliver, R.J.; Perrone-Bizzozero, N. HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes. Front. Genet. 2020, 11, 790. [Google Scholar] [CrossRef] [PubMed]
- Dell’Orco, M.; Elyaderani, A.; Vannan, A.; Sekar, S.; Powell, G.; Liang, W.S.; Neisewander, J.L.; Perrone-Bizzozero, N.I. HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction. Biology 2021, 10, 939. [Google Scholar] [CrossRef]
- Deschenes-Furry, J.; Mousavi, K.; Bolognani, F.; Neve, R.L.; Parks, R.J.; Perrone-Bizzozero, N.I.; Jasmin, B.J. The RNA–binding protein HuD binds acetylcholinesterase mRNA in neurons and regulates its expression after axotomy. J. Neurosci. 2007, 27, 665–675. [Google Scholar] [CrossRef] [Green Version]
- Amadio, M.; Pascale, A.; Wang, J.; Ho, L.; Quattrone, A.; Gandy, S.; Haroutunian, V.; Racchi, M.; Pasinetti, G.M. nELAV proteins alteration in Alzheimer’s disease brain: A novel putative target for amyloid-beta reverberating on AbetaPP processing. J. Alzheimers Dis. 2009, 16, 409–419. [Google Scholar] [CrossRef] [PubMed]
- Kang, M.-J.; Abdelmohsen, K.; Hutchison, E.R.; Mitchell, S.J.; Grammatikakis, I.; Guo, R.; Noh, J.H.; Martindale, J.L.; Yang, X.; Lee, E.K.; et al. HuD regulates coding and noncoding RNA to induce APP→Aβ processing. Cell Rep. 2014, 7, 1401–1409. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fragkouli, A.; Koukouraki, P.; Vlachos, I.S.; Paraskevopoulou, M.D.; Hatzigeorgiou, A.G.; Doxakis, E. Neuronal ELAVL proteins utilize AUF–1 as a co–partner to induce neuron–specific alternative splicing of APP. Sci. Rep. 2017, 7, 44507. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pastic, A.; Negeri, O.; Ravel-Chapuis, A.; Savard, A.; Trung, M.T.; Palidwor, G.; Guo, H.; Marcogliese, P.; Taylor, J.A.; Okano, H.; et al. LRRK2 Phosphorylates Neuronal Elav RNA-Binding Proteins to Regulate Phenotypes Relevant to Parkinson’s Disease. bioRxiv 2022. [Google Scholar] [CrossRef]
- Lim, C.S.; Alkon, D.L. Protein kinase C stimulates HuD–mediated mRNA stability and protein expression of neurotrophic factors and enhances dendritic maturation of hippocampal neurons in culture. Hippocampus 2012, 22, 2303–2319. [Google Scholar] [CrossRef]
- Sosanya, N.M.; Cacheaux, L.P.; Workman, E.R.; Niere, F.; Perrone-Bizzozero, N.I.; Raab-Graham, K.F. Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+/Calmodulin–dependent Protein Kinase II alpha (CaMKIIalpha) mRNAs by the RNA–binding Protein HuD. J. Biol. Chem. 2015, 290, 16357–16371. [Google Scholar] [CrossRef]
- Joseph, B.; Orlian, M.; Furneaux, H. p21(waf1) mRNA contains a conserved element in its 3′–untranslated region that is bound by the Elav–like mRNA–stabilizing proteins. J. Biol. Chem. 1998, 273, 20511–20516. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beckel-Mitchener, A.C.; Miera, A.; Keller, R.; Perrone-Bizzozero, N.I. Poly(A) tail length–dependent stabilization of GAP–43 mRNA by the RNA–binding protein HuD. J. Biol. Chem. 2002, 277, 27996–28002. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ince-Dunn, G.; Okano, H.J.; Jensen, K.B.; Park, W.Y.; Zhong, R.; Ule, J.; Mele, A.; Fak, J.J.; Yang, C.; Zhang, C.; et al. Neuronal Elav– like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability. Neuron 2012, 75, 1067–1080. [Google Scholar] [CrossRef] [Green Version]
- Ross, R.A.; Lazarova, D.L.; Manley, G.T.; Smitt, P.S.; Spengler, B.A.; Posner, J.B.; Biedler, J.L. HuD, a neuronal–specific RNA– binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells. Eur. J. Cancer 1997, 33, 2071–2074. [Google Scholar] [CrossRef] [PubMed]
- Manohar, C.F.; Short, M.L.; Nguyen, A.; Nguyen, N.N.; Chagnovich, D.; Yang, Q.; Cohn, S.L. HuD, a neuronal–specific RNA– binding protein, increases the in vivo stability of MYCN RNA. J. Biol. Chem. 2002, 277, 1967–1973. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Z.H.; Li, S.J.; Qi, Y.; Zhao, J.J.; Liu, X.Y.; Han, Y.; Xu, P.; Chen, X.H. HuD regulates the cpg15 expression via the 3′–UTR and AU–rich element. Neurochem. Res. 2011, 36, 1027–1036. [Google Scholar] [CrossRef]
- Zhu, H.; Hinman, M.N.; Hasman, R.A.; Mehta, P.; Lou, H. Regulation of neuron–specific alternative splicing of neurofibromatosis type 1 pre–mRNA. Mol. Cell Biol. 2008, 28, 1240–1251. [Google Scholar] [CrossRef] [Green Version]
- Zhou, H.L.; Hinman, M.N.; Barron, V.A.; Geng, C.; Zhou, G.; Luo, G.; Siegel, R.E.; Lou, H. Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA–dependent manner. Proc. Natl. Acad. Sci. USA 2011, 108, E627–E635. [Google Scholar] [CrossRef] [Green Version]
- Cuadrado, A.; Navarro-Yubero, C.; Furneaux, H.; Kinter, J.; Sonderegger, P.; Munoz, A. HuD binds to three AU–rich sequences in the 3′–UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein. Nucleic Acids Res. 2002, 30, 2202–2211. [Google Scholar] [CrossRef] [Green Version]
- Ratti, A.; Fallini, C.; Colombrita, C.; Pascale, A.; Laforenza, U.; Quattrone, A.; Silani, V. Post–transcriptional regulation of neuro–oncological ventral antigen 1 by the neuronal RNA–binding proteins ELAV. J. Biol. Chem. 2008, 283, 7531–7541. [Google Scholar] [CrossRef]
- Ratti, A.; Fallini, C.; Cova, L.; Fantozzi, R.; Calzarossa, C.; Zennaro, E.; Pascale, A.; Quattrone, A.; Silani, V. A role for the ELAV RNA–binding proteins in neural stem cells: Stabilization of Msi1 mRNA. J. Cell Sci. 2006, 119, 1442–1452. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sosanya, N.M.; Huang, P.P.C.; Cacheaux, L.P.; Chen, C.J.; Nguyen, K.; Perrone-Bizzozero, N.I.; Raab-Graham, K.F. Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR–129 repression by mTORCJ. Cell Biol. 2013, 202, 53–69. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, F.; Tidei, J.J.; Polich, E.D.; Gao, Y.; Zhao, H.; Perrone–Bizzozero, N.I.; Guo, W.; Zhao, X. Positive feedback between RNA– binding protein HuD and transcription factor SATB1 promotes neurogenesis. Proc. Natl. Acad. Sci. USA 2015, 112, E4995–E5004. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dell’Orco, M.; Sardone, V.; Gardiner, A.S.; Pansarasa, O.; Bordoni, M.; Perrone-Bizzozero, N.I.; Cereda, C. HuD regulates SOD1 expression during oxidative stress in differentiated neuroblastoma cells and sporadic ALS motor cortex. Neurobiol. Dis. 2021, 148, 105211. [Google Scholar] [CrossRef]
- Atlas, R.; Behar, L.; Elliott, E.; Ginzburg, I. The insulin–like growth factor mRNA binding–protein IMP–1 and the Ras–regulatory protein G3BP associate with tau mRNA and HuD protein in differentiated P19 neuronal cells. J. Neurochem. 2004, 89, 613–626. [Google Scholar] [CrossRef]
- Noureddine, M.A.; Qin, X.-J.; Oliveira, S.A.; Skelly, T.J.; van der Walt, J.; Hauser, M.A.; Pericak-Vance, M.A.; Vance, J.M.; Li, Y.-J. Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. Hum. Genet. 2005, 117, 27–33. [Google Scholar] [CrossRef]
- Haugarvoll, K.; Toft, M.; Ross, O.A.; Stone, J.T.; Heckman, M.G.; White, L.R.; Lynch, T.; Gibson, J.M.; Wszolek, Z.K.; Uitti, R.J.; et al. ELAVL4, PARK10, and the Celts. Mov. Disord. 2007, 22, 585–587. [Google Scholar] [CrossRef]
- DeStefano, A.L.; Latourelle, J.; Lew, M.F.; Suchowersky, O.; Klein, C.; Golbe, L.I.; Mark, M.H.; Growdon, J.H.; Wooten, G.F.; Watts, R.; et al. Replication of association between ELAVL4 and Parkinson disease: The GenePD study. Hum. Genet. 2008, 124, 95–99. [Google Scholar] [CrossRef] [Green Version]
- Pascale, A.; Amadio, M.; Scapagnini, G.; Lanni, C.; Racchi, M.; Provenzani, A.; Govoni, S.; Alkon, D.L.; Quattrone, A. Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway. Proc. Natl. Acad. Sci. USA 2005, 102, 12065–12070. [Google Scholar] [CrossRef] [Green Version]
- Subhadra, B.; Schaller, K.; Seeds, N.W. Neuroserpin up-regulation in the Alzheimer’s disease brain is associated with elevated thyroid hormone receptor-β1 and HuD expression. Neurochem. Int. 2013, 63, 476–481. [Google Scholar] [CrossRef]
- van der Linden, R.J.; Gerritsen, J.S.; Liao, M.; Widomska, J.; Pearse, R.V.; White, F.M.; Franke, B.; Young-Pearse, T.L.; Poelmans, G. RNA-binding protein ELAVL4/HuD ameliorates Alzheimer’s disease-related molecular changes in human iPSC-derived neurons. Prog. Neurobiol. 2022, 217, 102316. [Google Scholar] [CrossRef] [PubMed]
- Loffreda, A.; Nizzardo, M.; Arosio, A.; Ruepp, M.-D.; Calogero, R.A.; Volinia, S.; Galasso, M.; Bendotti, C.; Ferrarese, C.; Lunetta, C.; et al. miR-129-5p: A key factor and therapeutic target in amyotrophic lateral sclerosis. Prog. Neurobiol. 2020, 190, 101803. [Google Scholar] [CrossRef] [PubMed]
- De Santis, R.; Santini, L.; Colantoni, A.; Peruzzi, G.; de Turris, V.; Alfano, V.; Bozzoni, I.; Rosa, A. FUS Mutant Human Motoneurons Display Altered Transcriptome and microRNA Pathways with Implications for ALS Pathogenesis. Stem Cell Rep. 2017, 9, 1450–1462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garone, M.G.; Birsa, N.; Rosito, M.; Salaris, F.; Mochi, M.; de Turris, V.; Nair, R.R.; Cunningham, T.J.; Fisher, E.M.C.; Morlando, M.; et al. ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity. Commun. Biol. 2021, 4, 1025. [Google Scholar] [CrossRef] [PubMed]
- Blokhuis, A.M.; Koppers, M.; Groen, E.J.N.; van den Heuvel, D.M.A.; Dini Modigliani, S.; Anink, J.J.; Fumoto, K.; van Diggelen, F.; Snelting, A.; Sodaar, P.; et al. Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways. Acta Neuropathol. 2016, 132, 175–196. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Santis, R.; Alfano, V.; de Turris, V.; Colantoni, A.; Santini, L.; Garone, M.G.; Antonacci, G.; Peruzzi, G.; Sudria-Lopez, E.; Wyler, E.; et al. Mutant FUS and ELAVL4 (HuD) Aberrant Crosstalk in Amyotrophic Lateral Sclerosis. Cell Rep. 2019, 27, 3818–3831. e5. [Google Scholar] [CrossRef] [Green Version]
- Tolosa, E.; Garrido, A.; Scholz, S.W.; Poewe, W. Challenges in the diagnosis of Parkinson’s disease. Lancet Neurol. 2021, 20, 385–397. [Google Scholar] [CrossRef]
- Hubers, L.; Valderrama-Carvajal, H.; Laframboise, J.; Timbers, J.; Sanchez, G.; Côté, J. HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects. Hum. Mol. Genet. 2011, 20, 553–579. [Google Scholar] [CrossRef]
- Rohm, M.; May, C.; Marcus, K.; Steinbach, S.; Theis, V.; Theiss, C.; Matschke, V. The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis. Cell. Physiol. Biochem. 2019, 52, 1412–1426. [Google Scholar]
- Garone, M.G.; Alfano, V.; Salvatori, B.; Braccia, C.; Peruzzi, G.; Colantoni, A.; Bozzoni, I.; Armirotti, A.; Rosa, A. Proteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3’UTR binding. Sci. Rep. 2020, 10, 11827. [Google Scholar] [CrossRef]
- Birsa, N.; Ule, A.M.; Garone, M.G.; Tsang, B.; Mattedi, F.; Chong, P.A.; Humphrey, J.; Jarvis, S.; Pisiren, M.; Wilkins, O.G.; et al. FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation. Sci. Adv. 2021, 7, eabf8660. [Google Scholar] [CrossRef] [PubMed]
- Garone, M.G.; Salerno, D.; Rosa, A. Digital color-coded molecular barcoding reveals dysregulation of common FUS and FMRP targets in soma and neurites of ALS mutant motoneurons. bioRxiv 2022. [Google Scholar] [CrossRef]
- Tebaldi, T.; Zuccotti, P.; Peroni, D.; Köhn, M.; Gasperini, L.; Potrich, V.; Bonazza, V.; Dudnakova, T.; Rossi, A.; Sanguinetti, G.; et al. HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA. Mol. Cell. 2018, 71, 256–270.e10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Errichelli, L.; Dini Modigliani, S.; Laneve, P.; Colantoni, A.; Legnini, I.; Capauto, D.; Rosa, A.; De Santis, R.; Scarfò, R.; Peruzzi, G.; et al. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons. Nat. Commun. 2017, 8, 14741. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ripin, N.; Parker, R. Are stress granules the RNA analogs of misfolded protein aggregates? RNA 2022, 28, 67–75. [Google Scholar] [CrossRef]
- Barresi, V.; Musmeci, C.; Rinaldi, A.; Condorelli, D.F. Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets. Int. J. Mol. Sci. 2022, 23, 8875. [Google Scholar] [CrossRef] [PubMed]
- Mollasalehi, N.; Francois-Moutal, L.; Porciani, D.; Burke, D.H.; Khanna, M. Aptamers Targeting Hallmark Proteins of Neurodegeneration. Nucleic Acid. Ther. 2022, 32, 235–250. [Google Scholar] [CrossRef] [PubMed]
- Zacco, E.; Kantelberg, O.; Milanetti, E.; Armaos, A.; Panei, F.P.; Gregory, J.; Jeacock, K.; Clarke, D.J.; Chandran, S.; Ruocco, G.; et al. Probing TDP-43 condensation using an in silico designed aptamer. Nat. Commun. 2022, 13, 3306. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Hu, C.; Moufawad El Achkar, C.; Black, L.E.; Douville, J.; Larson, A.; Pendergast, M.K.; Goldkind, S.F.; Lee, E.A.; Kuniholm, A.; et al. Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease. N. Engl. J. Med. 2019, 381, 1644–1652. [Google Scholar] [CrossRef]
Target | Region | Sequence | Regulatory Mechanism | Function | Reference |
---|---|---|---|---|---|
AChE | 3’UTR | AU-rich element | mRNA stability | + | [10] |
AChE | 3’UTR | AU-rich element | mRNA stability | + | [24] |
ADAM10 | 3’UTR | AU-rich element | mRNA stability | + | [25] |
APP | 3’UTR | mRNA stability | + | [26] | |
APP | Intron | U-rich element | Alternative splicing | + | [27] |
α-synuclein (SNCA) | 3’UTR | U-rich element | + | [28] | |
BACE1 | 3’UTR | U-rich element | mRNA stability | + | [26] |
BACE-AS | - | U-rich element | + | [26] | |
BDNF | 3’UTR | AU-rich element | mRNA stability | + | [29] |
CGPR | Intron | U-rich element | Alternative splicing | + | [20] |
CaMKIIα | 3’UTR | AU-rich element | mRNA stability | + | [30] |
CDKN1A | 3’UTR | U-rich element | mRNA stability | + | [31] |
cirHomer1a | - | AU-rich element | Expression and transport | + | [22] |
GAP-43 | 3’UTR | AU-rich element | mRNA stability | + | [32] |
GAP-44 | 3’UTR | AU-rich element | Transport | + | [13] |
Gls | Intron | GU-rich element | Alternative splicing | - | [33] |
LRRK2 | 3’UTR | U-rich element | + | [28] | |
MYCN | 3’UTR | AU-rich element | mRNA stability | + | [34] |
MYCN | 3’UTR | AU-rich element | mRNA stability | + | [35] |
NEP | 3’UTR | AU-rich element | mRNA stability | + | [29] |
NGF | 3’UTR | AU-rich element | mRNA stability | + | [29] |
Neuritin 1 | 3’UTR | AU-rich element | Localization | + | [9] |
Neuritin 1 | 3’UTR | AU-rich element | Localization | + | [14] |
Neuritin 1 | 3’UTR | AU-rich element | mRNA stability | + | [36] |
NF–1 | Intron | AU-rich element | Alternative splicing | + | [37] |
NF–1 | Intron | AU-rich element | Local transcription elongation | + | [38] |
Neuroserpin | 3’UTR | AU-rich element | mRNA stability | + | [39] |
NT-3 | 3’UTR | AU-rich element | mRNA stability | + | [29] |
NOVA–1 | 3’UTR | AU-rich element | mRNA stability and Translation | + | [40] |
MSI1 | 3’UTR | AU-rich element | mRNA stability | + | [41] |
Kv1.1 | coding region | U-rich element | Translation | + | [42] |
SATB1 | 3’UTR | AU-rich element | mRNA stability | + | [43] |
SOD1 | 3’UTR | AU-rich element | mRNA stability | + | [44] |
Tau | 3’UTR | U-rich element | Transport | + | [45] |
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Silvestri, B.; Mochi, M.; Garone, M.G.; Rosa, A. Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases. Int. J. Mol. Sci. 2022, 23, 14606. https://doi.org/10.3390/ijms232314606
Silvestri B, Mochi M, Garone MG, Rosa A. Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases. International Journal of Molecular Sciences. 2022; 23(23):14606. https://doi.org/10.3390/ijms232314606
Chicago/Turabian StyleSilvestri, Beatrice, Michela Mochi, Maria Giovanna Garone, and Alessandro Rosa. 2022. "Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases" International Journal of Molecular Sciences 23, no. 23: 14606. https://doi.org/10.3390/ijms232314606
APA StyleSilvestri, B., Mochi, M., Garone, M. G., & Rosa, A. (2022). Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases. International Journal of Molecular Sciences, 23(23), 14606. https://doi.org/10.3390/ijms232314606