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Neurite-Enriched MicroRNA-218 Stimulates Translation of the GluA2 Subunit and Increases Excitatory Synaptic Strength

  • Anna RocchiEmail author
  • Daniela Moretti
  • Gabriele Lignani
  • Elisabetta Colombo
  • Joachim Scholz-Starke
  • Pietro Baldelli
  • Tatiana Tkatch
  • Fabio Benfenati
Article

Abstract

Local control of protein translation is a fundamental process for the regulation of synaptic plasticity. It has been demonstrated that the local protein synthesis occurring in axons and dendrites can be shaped by numerous mechanisms, including miRNA-mediated regulation. However, several aspects underlying this regulatory process have not been elucidated yet. Here, we analyze the differential miRNA profile in cell bodies and neurites of primary hippocampal neurons and find an enrichment of the precursor and mature forms of miR-218 in the neuritic projections. We show that miR-218 abundance is regulated during hippocampal development and by chronic silencing or activation of neuronal network. Overexpression and knockdown of miR-218 demonstrated that miR-218 targets the mRNA encoding the GluA2 subunit of AMPA receptors and modulates its expression. At the functional level, miR-218 overexpression increases glutamatergic synaptic transmission at both single neuron and network levels. Our data demonstrate that miR-218 may play a key role in the regulation of AMPA-mediated excitatory transmission and in the homeostatic regulation of synaptic plasticity.

Keywords

GluA2 Homeostatic plasticity Local translation Neurite-specific microRNAs 

Notes

Acknowledgements

We thank Luigi Naldini for kindly providing lentiviral vectors; Monica Morini, Riccardo Navone (Italian Institute of Technology, Genova, Italy), and Michele Cilli (IRCCS San Martino, Genova, Italy) for help in breeding the mice; and Arta Mehilli (Center for Synaptic Neuroscience, Istituto Italiano di Tecnologia, Genova, Italy) for assistance in the preparation of primary cultures. This study was supported by research grants from Compagnia di San Paolo (2015.0546 to FB and 2017.0589 to PB), EU FP7 Project “Desire” (Grant agreement n. 602531 to FB) and the Italian Ministry of Health Ricerca Finalizzata (GR-2013-02355540 to AR).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1492_Fig5_ESM.png (109 kb)
Fig. S1

Specificity of the effects of miR-218 on GluA2 3′UTR in HEK293T cells. (A) Luciferase expression was used to monitor the dose-dependent effect of miR-218 mimic on GluA2 3’UTR in HEK293T cells that do not endogenously express GluA2. Scr, scrambled miRNA control. (B) Effect of miR-218 and miR-218 inhibitor (anti-miR-218) on the wild type and mutated forms of Gria2 3′UTR. Data are shown as means ± sem (n = 4). * p < 0.05, ** p < 0.01; unpaired Student’s t test. (PNG 108 kb)

12035_2019_1492_MOESM1_ESM.tif (37.6 mb)
High Resolution Image (TIF 38480 kb)
12035_2019_1492_Fig7_ESM.png (26 kb)
Fig. S2

Luciferase mRNA is not affected by miR-218 overexpression. Real time PCR analysis of luciferase transcript level in hippocampal neurons overexpressing miR-218 mimic as compared to the respective scrambled sequence (Scr). Data are shown as means ± sem (n = 4). (PNG 26 kb)

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High Resolution Image (TIF 4890 kb)
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Fig. S3

The effects of miR-218 on network activity are mediated by an increase in AMPA transmission. (A) Representative raster plots of the network electrical activity recorded in neurons expressing scrambled sequence (black), miR-218 (red) or miR-218 (green) in presence of the specific AMPA glutamate receptor inhibitor CNQX (20 μM) . (B) The overall activity of the network under the various experimental conditions is expressed as the cumulative firing rates recorded over a period of 200 s (Hz) weighted on the number of active electrodes. Data are means ± sem (n = 3 independent preparations). * p < 0.05; ** p < 0.01; one-way ANOVA/Bonferroni’s multiple comparison test. (PNG 153 kb)

12035_2019_1492_MOESM3_ESM.tif (42 mb)
High Resolution Image (TIF 42968 kb)
12035_2019_1492_MOESM4_ESM.xlsx (11 kb)
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ESM 2 (XLSX 10 kb)

References

  1. 1.
    Cajigas IJ, Will T, Schuman EM (2010) Protein homeostasis and synaptic plasticity. EMBO J 29(16):2746–2752.  https://doi.org/10.1038/emboj.2010.173 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yi JJ, Ehlers MD (2005) Ubiquitin and protein turnover in synapse function. Neuron 47(5):629–632.  https://doi.org/10.1016/j.neuron.2005.07.008 CrossRefPubMedGoogle Scholar
  3. 3.
    Holt CE, Schuman EM (2013) The central dogma decentralized: new perspectives on RNA function and local translation in neurons. Neuron 80(3):648–657.  https://doi.org/10.1016/j.neuron.2013.10.036 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Martin KC, Ephrussi A (2009) mRNA localization: gene expression in the spatial dimension. Cell 136(4):719–730.  https://doi.org/10.1016/j.cell.2009.01.044 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Richter JD, Klann E (2009) Making synaptic plasticity and memory last: mechanisms of translational regulation. Genes Dev 23(1):1–11.  https://doi.org/10.1101/gad.1735809 CrossRefPubMedGoogle Scholar
  6. 6.
    Sutton MA, Ito HT, Cressy P, Kempf C, Woo JC, Schuman EM (2006) Miniature neurotransmission stabilizes synaptic function via tonic suppression of local dendritic protein synthesis. Cell 125(4):785–799.  https://doi.org/10.1016/j.cell.2006.03.040 CrossRefPubMedGoogle Scholar
  7. 7.
    Cox DJ, Racca C (2013) Differential dendritic targeting of AMPA receptor subunit mRNAs in adult rat hippocampal principal neurons and interneurons. J Comp Neurol 521(9):1954–2007.  https://doi.org/10.1002/cne.23292 CrossRefPubMedGoogle Scholar
  8. 8.
    Ostroff LE, Fiala JC, Allwardt B, Harris KM (2002) Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices. Neuron 35(3):535–545CrossRefGoogle Scholar
  9. 9.
    Steward O, Levy WB (1982) Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J Neurosci 2(3):284–291CrossRefGoogle Scholar
  10. 10.
    Vessey JP, Vaccani A, Xie Y, Dahm R, Karra D, Kiebler MA, Macchi P (2006) Dendritic localization of the translational repressor Pumilio 2 and its contribution to dendritic stress granules. J Neurosci 26(24):6496–6508.  https://doi.org/10.1523/JNEUROSCI.0649-06.2006 CrossRefPubMedGoogle Scholar
  11. 11.
    Ferrari F, Mercaldo V, Piccoli G, Sala C, Cannata S, Achsel T, Bagni C (2007) The fragile X mental retardation protein-RNP granules show an mGluR-dependent localization in the post-synaptic spines. Mol Cell Neurosci 34(3):343–354.  https://doi.org/10.1016/j.mcn.2006.11.015 CrossRefPubMedGoogle Scholar
  12. 12.
    Lugli G, Larson J, Martone ME, Jones Y, Smalheiser NR (2005) Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. J Neurochem 94(4):896–905.  https://doi.org/10.1111/j.1471-4159.2005.03224.x CrossRefPubMedGoogle Scholar
  13. 13.
    Rao A, Steward O (1991) Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes. J Neurosci 11(9):2881–2895CrossRefGoogle Scholar
  14. 14.
    Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642–655.  https://doi.org/10.1016/j.cell.2009.01.035 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (2004) Processing of primary microRNAs by the microprocessor complex. Nature 432(7014):231–235.  https://doi.org/10.1038/nature03049 CrossRefPubMedGoogle Scholar
  16. 16.
    Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20):4051–4060.  https://doi.org/10.1038/sj.emboj.7600385 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297CrossRefGoogle Scholar
  18. 18.
    Ye Y, Xu H, Su X, He X (2016) Role of microRNA in governing synaptic plasticity. Neural Plast 2016:4959523.  https://doi.org/10.1155/2016/4959523 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439(7074):283–289.  https://doi.org/10.1038/nature04367 CrossRefPubMedGoogle Scholar
  20. 20.
    Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF et al (2009) A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol 11(6):705–716.  https://doi.org/10.1038/ncb1876 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fiore R, Rajman M, Schwale C, Bicker S, Antoniou A, Bruehl C, Draguhn A, Schratt G (2014) MiR-134-dependent regulation of Pumilio-2 is necessary for homeostatic synaptic depression. EMBO J 33(19):2231–2246.  https://doi.org/10.15252/embj.201487921 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kye MJ, Liu T, Levy SF, Xu NL, Groves BB, Bonneau R, Lao K, Kosik KS (2007) Somatodendritic microRNAs identified by laser capture and multiplex RT-PCR. Rna 13(8):1224–1234.  https://doi.org/10.1261/rna.480407 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lugli G, Torvik VI, Larson J, Smalheiser NR (2008) Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain. J Neurochem 106(2):650–661.  https://doi.org/10.1111/j.1471-4159.2008.05413.x CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Natera-Naranjo O, Aschrafi A, Gioio AE, Kaplan BB (2010) Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons. Rna 16(8):1516–1529.  https://doi.org/10.1261/rna.1833310 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Sasaki Y, Gross C, Xing L, Goshima Y, Bassell GJ (2014) Identification of axon-enriched microRNAs localized to growth cones of cortical neurons. Dev Neurobiol 74(3):397–406.  https://doi.org/10.1002/dneu.22113 CrossRefPubMedGoogle Scholar
  26. 26.
    Grooms SY, Noh KM, Regis R, Bassell GJ, Bryan MK, Carroll RC, Zukin RS (2006) Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of hippocampal neurons. J Neurosci 26(32):8339–8351.  https://doi.org/10.1523/JNEUROSCI.0472-06.2006 CrossRefPubMedGoogle Scholar
  27. 27.
    Lignani G, Raimondi A, Ferrea E, Rocchi A, Paonessa F, Cesca F, Orlando M, Tkatch T et al (2013) Epileptogenic Q555X SYN1 mutant triggers imbalances in release dynamics and short-term plasticity. Hum Mol Genet 22(11):2186–2199.  https://doi.org/10.1093/hmg/ddt071 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):RESEARCH0034CrossRefGoogle Scholar
  29. 29.
    Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39(10):1278–1284.  https://doi.org/10.1038/ng2135 CrossRefPubMedGoogle Scholar
  30. 30.
    Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20.  https://doi.org/10.1016/j.cell.2004.12.035 CrossRefPubMedGoogle Scholar
  31. 31.
    Lall S, Grun D, Krek A, Chen K, Wang YL, Dewey CN, Sood P, Colombo T et al (2006) A genome-wide map of conserved microRNA targets in C. elegans. Curr Biol 16(5):460–471.  https://doi.org/10.1016/j.cub.2006.01.050 CrossRefPubMedGoogle Scholar
  32. 32.
    McSweeney KM, Gussow AB, Bradrick SS, Dugger SA, Gelfman S, Wang Q, Petrovski S, Frankel WN et al (2016) Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks. Genome Res 26(10):1411–1416.  https://doi.org/10.1101/gr.199828.115 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chiappalone M, Novellino A, Vajda I, Vato A, Martinoia S, Van Pelt J (2005) Burst detection algorithms for the analysis of spatio-temporal patterns in cortical networks of neurons. Neurocomputing 65-66:653–662CrossRefGoogle Scholar
  34. 34.
    Torre ER, Steward O (1992) Demonstration of local protein synthesis within dendrites using a new cell culture system that permits the isolation of living axons and dendrites from their cell bodies. J Neurosci 12(3):762–772CrossRefGoogle Scholar
  35. 35.
    Poon MM, Choi SH, Jamieson CA, Geschwind DH, Martin KC (2006) Identification of process-localized mRNAs from cultured rodent hippocampal neurons. J Neurosci 26(51):13390–13399.  https://doi.org/10.1523/JNEUROSCI.3432-06.2006 CrossRefPubMedGoogle Scholar
  36. 36.
    Kohler A, Hurt E (2007) Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell Biol 8(10):761–773.  https://doi.org/10.1038/nrm2255 CrossRefPubMedGoogle Scholar
  37. 37.
    Litman P, Barg J, Ginzburg I (1994) Microtubules are involved in the localization of tau mRNA in primary neuronal cell cultures. Neuron 13(6):1463–1474CrossRefGoogle Scholar
  38. 38.
    Bicker S, Khudayberdiev S, Weiss K, Zocher K, Baumeister S, Schratt G (2013) The DEAH-box helicase DHX36 mediates dendritic localization of the neuronal precursor-microRNA-134. Genes Dev 27(9):991–996.  https://doi.org/10.1101/gad.211243.112 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Bramham CR, Wells DG (2007) Dendritic mRNA: transport, translation and function. Nat Rev Neurosci 8(10):776–789.  https://doi.org/10.1038/nrn2150 CrossRefPubMedGoogle Scholar
  40. 40.
    Sambandan S, Akbalik G, Kochen L, Rinne J, Kahlstatt J, Glock C, Tushev G, Alvarez-Castelao B et al (2017) Activity-dependent spatially localized miRNA maturation in neuronal dendrites. Science 355(6325):634–637.  https://doi.org/10.1126/science.aaf8995 CrossRefPubMedGoogle Scholar
  41. 41.
    Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I et al (2005) Combinatorial microRNA target predictions. Nat Genet 37(5):495–500.  https://doi.org/10.1038/ng1536 CrossRefPubMedGoogle Scholar
  42. 42.
    Ju W, Morishita W, Tsui J, Gaietta G, Deerinck TJ, Adams SR, Garner CC, Tsien RY et al (2004) Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors. Nat Neurosci 7(3):244–253.  https://doi.org/10.1038/nn1189nn1189 CrossRefPubMedGoogle Scholar
  43. 43.
    Saba R, Storchel PH, Aksoy-Aksel A, Kepura F, Lippi G, Plant TD, Schratt GM (2012) Dopamine-regulated microRNA MiR-181a controls GluA2 surface expression in hippocampal neurons. Mol Cell Biol 32(3):619–632.  https://doi.org/10.1128/MCB.05896-11 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Harraz MM, Eacker SM, Wang X, Dawson TM, Dawson VL (2012) MicroRNA-223 is neuroprotective by targeting glutamate receptors. Proc Natl Acad Sci U S A 109(46):18962–18967.  https://doi.org/10.1073/pnas.1121288109 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Dutta R, Chomyk AM, Chang A, Ribaudo MV, Deckard SA, Doud MK, Edberg DD, Bai B et al (2013) Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors. Ann Neurol 73(5):637–645.  https://doi.org/10.1002/ana.23860 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Gascon E, Lynch K, Ruan H, Almeida S, Verheyden JM, Seeley WW, Dickson DW, Petrucelli L et al (2014) Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med 20(12):1444–1451.  https://doi.org/10.1038/nm.3717 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ho VM, Dallalzadeh LO, Karathanasis N, Keles MF, Vangala S, Grogan T, Poirazi P, Martin KC (2014) GluA2 mRNA distribution and regulation by miR-124 in hippocampal neurons. Mol Cell Neurosci 61:1–12.  https://doi.org/10.1016/j.mcn.2014.04.006 CrossRefPubMedGoogle Scholar
  48. 48.
    Hou Q, Ruan H, Gilbert J, Wang G, Ma Q, Yao WD, Man HY (2015) MicroRNA miR124 is required for the expression of homeostatic synaptic plasticity. Nat Commun 6:10045.  https://doi.org/10.1038/ncomms10045 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H et al (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62(3):405–496.  https://doi.org/10.1124/pr.109.002451 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Tanaka H, Grooms SY, Bennett MV, Zukin RS (2000) The AMPAR subunit GluR2: still front and center-stage. Brain Res 886(1–2):190–207CrossRefGoogle Scholar
  51. 51.
    Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126.  https://doi.org/10.1146/annurev.neuro.25.112701.142758 CrossRefGoogle Scholar
  52. 52.
    Isaac JT, Ashby MC, McBain CJ (2007) The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron 54(6):859–871.  https://doi.org/10.1016/j.neuron.2007.06.001 CrossRefPubMedGoogle Scholar
  53. 53.
    Riedel G, Micheau J, Lam AG, Roloff EL, Martin SJ, Bridge H, de Hoz L, Poeschel B et al (1999) Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat Neurosci 2(10):898–905.  https://doi.org/10.1038/13202 CrossRefPubMedGoogle Scholar
  54. 54.
    Wiltgen BJ, Royle GA, Gray EE, Abdipranoto A, Thangthaeng N, Jacobs N, Saab F, Tonegawa S et al (2010) A role for calcium-permeable AMPA receptors in synaptic plasticity and learning. PLoS One 5(9):e12818.  https://doi.org/10.1371/journal.pone.0012818 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Kacharmina JE, Job C, Crino P, Eberwine J (2000) Stimulation of glutamate receptor protein synthesis and membrane insertion within isolated neuronal dendrites. Proc Natl Acad Sci U S A 97(21):11545–11550. https://doi.org/10.1073/pnas.97.21.1154597/21/11545[pii]Google Scholar
  56. 56.
    Beveridge NJ, Tooney PA, Carroll AP, Gardiner E, Bowden N, Scott RJ, Tran N, Dedova I et al (2008) Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet 17(8):1156–1168.  https://doi.org/10.1093/hmg/ddn005 CrossRefPubMedGoogle Scholar
  57. 57.
    Lonardoni D, Amin H, Di Marco S, Maccione A, Berdondini L, Nieus T (2017) Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks. PLoS Comput Biol 13(7):e1005672.  https://doi.org/10.1371/journal.pcbi.1005672 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Ancona Esselmann SG, Diaz-Alonso J, Levy JM, Bemben MA, Nicoll RA (2017) Synaptic homeostasis requires the membrane-proximal carboxy tail of GluA2. Proc Natl Acad Sci U S A 114(50):13266–13271.  https://doi.org/10.1073/pnas.1716022114 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Anggono V, Clem RL, Huganir RL (2011) PICK1 loss of function occludes homeostatic synaptic scaling. J Neurosci 31(6):2188–2196.  https://doi.org/10.1523/JNEUROSCI.5633-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Diering GH, Gustina AS, Huganir RL (2014) PKA-GluA1 coupling via AKAP5 controls AMPA receptor phosphorylation and cell-surface targeting during bidirectional homeostatic plasticity. Neuron 84(4):790–805.  https://doi.org/10.1016/j.neuron.2014.09.024 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Wierenga CJ, Ibata K, Turrigiano GG (2005) Postsynaptic expression of homeostatic plasticity at neocortical synapses. J Neurosci 25(11):2895–2905.  https://doi.org/10.1523/JNEUROSCI.5217-04.2005 CrossRefPubMedGoogle Scholar
  62. 62.
    Lussier MP, Nasu-Nishimura Y, Roche KW (2011) Activity-dependent ubiquitination of the AMPA receptor subunit GluA2. J Neurosci 31(8):3077–3081.  https://doi.org/10.1523/JNEUROSCI.5944-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Jensen V, Kaiser KM, Borchardt T, Adelmann G, Rozov A, Burnashev N, Brix C, Frotscher M et al (2003) A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A. J Physiol 553(Pt 3):843–856.  https://doi.org/10.1113/jphysiol.2003.053637 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Monyer H, Seeburg PH, Wisden W (1991) Glutamate-operated channels: developmentally early and mature forms arise by alternative splicing. Neuron 6(5):799–810CrossRefGoogle Scholar
  65. 65.
    Jonas S, Izaurralde E (2015) Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 16(7):421–433.  https://doi.org/10.1038/nrg3965 CrossRefPubMedGoogle Scholar
  66. 66.
    Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309(5740):1577–1581.  https://doi.org/10.1126/science.1113329 CrossRefPubMedGoogle Scholar
  67. 67.
    Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318(5858):1931–1934.  https://doi.org/10.1126/science.1149460 CrossRefPubMedGoogle Scholar
  68. 68.
    Mortensen RD, Serra M, Steitz JA, Vasudevan S (2011) Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc Natl Acad Sci U S A 108(20):8281–8286.  https://doi.org/10.1073/pnas.1105401108 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Valinezhad Orang A, Safaralizadeh R, Kazemzadeh-Bavili M (2014) Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genomics 2014:970607.  https://doi.org/10.1155/2014/970607 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Bukhari SIA, Truesdell SS, Lee S, Kollu S, Classon A, Boukhali M, Jain E, Mortensen RD et al (2016) A specialized mechanism of translation mediated by FXR1a-associated microRNP in cellular quiescence. Mol Cell 61(5):760–773.  https://doi.org/10.1016/j.molcel.2016.02.013 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Vasudevan S (2012) Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA 3(3):311–330.  https://doi.org/10.1002/wrna.121 CrossRefPubMedGoogle Scholar
  72. 72.
    Liu JJ, Zhao CM, Li ZG, Wang YM, Miao W, Wu XJ, Wang WJ, Liu C et al (2016) miR-218 involvement in cardiomyocyte hypertrophy is likely through targeting REST. Int J Mol Sci 17(6):848.  https://doi.org/10.3390/ijms17060848 CrossRefPubMedCentralGoogle Scholar
  73. 73.
    Myers SJ, Peters J, Huang Y, Comer MB, Barthel F, Dingledine R (1998) Transcriptional regulation of the GluR2 gene: neural-specific expression, multiple promoters, and regulatory elements. J Neurosci 18(17):6723–6739CrossRefGoogle Scholar
  74. 74.
    Calderone A, Jover T, Noh KM, Tanaka H, Yokota H, Lin Y, Grooms SY, Regis R et al (2003) Ischemic insults derepress the gene silencer REST in neurons destined to die. J Neurosci 23(6):2112–2121CrossRefGoogle Scholar
  75. 75.
    Pozzi D, Lignani G, Ferrea E, Contestabile A, Paonessa F, D'Alessandro R, Lippiello P, Boido D et al (2013) REST/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability. EMBO J 32(22):2994–3007.  https://doi.org/10.1038/emboj.2013.231 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Pecoraro-Bisogni F, Lignani G, Contestabile A, Castroflorio E, Pozzi D, Rocchi A, Prestigio C, Orlando M et al (2018) REST-dependent presynaptic homeostasis induced by chronic neuronal hyperactivity. Mol Neurobiol 55(6):4959–4972.  https://doi.org/10.1007/s12035-017-0698-9 CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Center for Synaptic Neuroscience and TechnologyIstituto Italiano di TecnologiaGenoaItaly
  2. 2.IRCSS Ospedale Policlinico San MartinoGenoaItaly
  3. 3.Department of Experimental Medicine, Section of PhysiologyUniversity of GenoaGenoaItaly
  4. 4.Institute of Neurology, Department of Clinical and Experimental EpilepsyUniversity College LondonLondonUK
  5. 5.Consiglio Nazionale delle RicercheInstitute of BiophysicsGenoaItaly

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