In Vivo Translatome Profiling in Spinal Muscular Atrophy Reveals a Role for SMN Protein in Ribosome Biology

Cell Reports

Volumn 21, Issue 4, 2017, Pages 953-965

  Bernabò, Paola ^a   Tebaldi, Toma ^b   Groen, Ewout J N ^c,d   Lane, Fiona M ^c,d   Perenthaler, Elena ^a   Mattedi, Francesca ^a   Newbery, Helen J ^c,d   Zhou, Haiyan ^e   Zuccotti, Paola ^b   Potrich, Valentina ^b   Shorrock, Hannah K ^c,d   Muntoni, Francesco ^e   Quattrone, Alessandro ^b   Gillingwater, Thomas H ^c,d   Viero, Gabriella ^a  

^a CNR   (Italy)

^b UNIVERSITY OF TRENTO   (Italy)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d UNIVERSITY OF EDINBURGH   (United Kingdom)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

motor neuron disease; neurodegeneration; polysomal profiling; ribosome; SMN; spinal muscular atrophy; translatome

Indexed keywords

SURVIVAL MOTOR NEURON PROTEIN; PROTEOME; SMN1 PROTEIN, MOUSE; SURVIVAL MOTOR NEURON PROTEIN 1; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CRISPR-CAS9 SYSTEM; GENETIC ANALYSIS; GENETIC TRANSCRIPTION; IN VITRO STUDY; IN VIVO STUDY; MOTOR PERFORMANCE; MOUSE; NERVE CELL DEGENERATION; NEWBORN; NEXT GENERATION SEQUENCING; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; QUANTITATIVE ANALYSIS; RIBOSOME; RNA TRANSLATION; SPINAL MUSCULAR ATROPHY; WESTERN BLOTTING; ANIMAL; CELL CULTURE; GENETICS; METABOLISM; MOTONEURON; POLYSOME; PROTEIN SYNTHESIS;

ANIMALS; CELLS, CULTURED; MICE; MOTOR NEURONS; MUSCULAR ATROPHY, SPINAL; POLYRIBOSOMES; PROTEIN BIOSYNTHESIS; PROTEOME; SURVIVAL OF MOTOR NEURON 1 PROTEIN; TRANSCRIPTOME;

EID: 85032016119     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2017.10.010     Document Type: Article

References (79)

1. Anand, M., Chakraburtty, K., Marton, M.J., Hinnebusch, A.G., Kinzy, T.G., Functional interactions between yeast translation eukaryotic elongation factor (eEF) 1A and eEF3. J. Biol. Chem. 278 (2003), 6985–6991.
2. Bäumer, D., Lee, S., Nicholson, G., Davies, J.L., Parkinson, N.J., Murray, L.M., Gillingwater, T.H., Ansorge, O., Davies, K.E., Talbot, K., Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genet., 5, 2009, e1000773.
3. Béchade, C., Rostaing, P., Cisterni, C., Kalisch, R., La Bella, V., Pettmann, B., Triller, A., Subcellular distribution of survival motor neuron (SMN) protein: possible involvement in nucleocytoplasmic and dendritic transport. Eur. J. Neurosci. 11 (1999), 293–304.
4. 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. 132 (2016), 175–196.
5. Brina, D., Miluzio, A., Ricciardi, S., Clarke, K., Davidsen, P.K., Viero, G., Tebaldi, T., Offenhäuser, N., Rozman, J., Rathkolb, B., et al. eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription. Nat. Commun., 6, 2015, 8261.
6. Brinegar, A.E., Cooper, T.A., Roles for RNA-binding proteins in development and disease. Brain Res. 1647 (2016), 1–8.
7. Burghes, A.H.M., Beattie, C.E., Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?. Nat. Rev. Neurosci. 10 (2009), 597–609.
8. Carlevaro-Fita, J., Rahim, A., Guigó, R., Vardy, L.A., Johnson, R., Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells. RNA 22 (2016), 867–882.
9. Casellas, J., Inbred mouse strains and genetic stability: a review. Animal 5 (2011), 1–7.
10. Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P.D., Wu, X., Jiang, W., Marraffini, L.A., et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339 (2013), 819–823.
11. Cookson, M.R., RNA-binding proteins implicated in neurodegenerative diseases. Wiley Interdiscip. Rev. RNA, 2016, 10.1002/wrna.1397 Published online September 23, 2016.
12. Coyne, A.N., Siddegowda, B.B., Estes, P.S., Johannesmeyer, J., Kovalik, T., Daniel, S.G., Pearson, A., Bowser, R., Zarnescu, D.C., Futsch/MAP1B mRNA is a translational target of TDP-43 and is neuroprotective in a Drosophila model of amyotrophic lateral sclerosis. J. Neurosci. 34 (2014), 15962–15974.
13. Coyne, A.N., Yamada, S.B., Siddegowda, B.B., Estes, P.S., Zaepfel, B.L., Johannesmeyer, J.S., Lockwood, D.B., Pham, L.T., Hart, M.P., Cassel, J.A., et al. Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation. Hum. Mol. Genet. 24 (2015), 6886–6898.
14. Darnell, J.C., Van Driesche, S.J., Zhang, C., Hung, K.Y.S., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W., et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146 (2011), 247–261.
15. Dieterich, D.C., Hodas, J.J.L., Gouzer, G., Shadrin, I.Y., Ngo, J.T., Triller, A., Tirrell, D.A., Schuman, E.M., In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat. Neurosci. 13 (2010), 897–905.
16. Ding, Q., Markesbery, W.R., Chen, Q., Li, F., Keller, J.N., Ribosome dysfunction is an early event in Alzheimer's disease. J. Neurosci. 25 (2005), 9171–9175.
17. Doktor, T.K., Hua, Y., Andersen, H.S., Brøner, S., Liu, Y.H., Wieckowska, A., Dembic, M., Bruun, G.H., Krainer, A.R., Andresen, B.S., RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns. Nucleic Acids Res. 45 (2016), 395–416.
18. Donlin-Asp, P.G., Bassell, G.J., Rossoll, W., A role for the survival of motor neuron protein in mRNP assembly and transport. Curr. Opin. Neurobiol. 39 (2016), 53–61.
19. Dragon, F., Gallagher, J.E.G., Compagnone-Post, P.A., Mitchell, B.M., Porwancher, K.A., Wehner, K.A., Wormsley, S., Settlage, R.E., Shabanowitz, J., Osheim, Y., et al. A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis. Nature 417 (2002), 967–970.
20. Eaton, S.L., Roche, S.L., Llavero Hurtado, M., Oldknow, K.J., Farquharson, C., Gillingwater, T.H., Wishart, T.M., Total protein analysis as a reliable loading control for quantitative fluorescent Western blotting. PLoS ONE, 8, 2013, e72457.
21. Fallini, C., Zhang, H., Su, Y., Silani, V., Singer, R.H., Rossoll, W., Bassell, G.J., The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons. J. Neurosci. 31 (2011), 3914–3925.
22. Fallini, C., Bassell, G.J., Rossoll, W., Spinal muscular atrophy: the role of SMN in axonal mRNA regulation. Brain Res. 1462 (2012), 81–92.
23. Fallini, C., Donlin-Asp, P.G., Rouanet, J.P., Bassell, G.J., Rossoll, W., Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons. J. Neurosci. 36 (2016), 3811–3820.
24. Farrar, M.A., Park, S.B., Vucic, S., Carey, K.A., Turner, B.J., Gillingwater, T.H., Swoboda, K.J., Kiernan, M.C., Emerging therapies and challenges in spinal muscular atrophy. Ann. Neurol. 81 (2017), 355–368.
25. Fuller, H.R., Man, N.T., Lam, T., Thanh, T., Keough, R.A., Asperger, A., Gonda, T.J., Morris, G.E., The SMN interactome includes Myb-binding protein 1a. J. Proteome Res. 9 (2010), 556–563.
26. Gabanella, F., Pisani, C., Borreca, A., Farioli-Vecchioli, S., Ciotti, M.T., Ingegnere, T., Onori, A., Ammassari-Teule, M., Corbi, N., Canu, N., et al. SMN affects membrane remodelling and anchoring of the protein synthesis machinery. J. Cell Sci. 129 (2016), 804–816.
27. Groen, E.J.N., Gillingwater, T.H., UBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration. Trends Mol. Med. 21 (2015), 622–632.
28. Groen, E.J.N., Fumoto, K., Blokhuis, A.M., Engelen-Lee, J., Zhou, Y., van den Heuvel, D.M.A., Koppers, M., van Diggelen, F., van Heest, J., Demmers, J.A.A., et al. ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN. Hum. Mol. Genet. 22 (2013), 3690–3704.
29. Hamilton, G., Gillingwater, T.H., Spinal muscular atrophy: going beyond the motor neuron. Trends Mol. Med. 19 (2013), 40–50.
30. Hsieh-Li, H.M., Chang, J.G., Jong, Y.J., Wu, M.H., Wang, N.M., Tsai, C.H., Li, H., A mouse model for spinal muscular atrophy. Nat. Genet. 24 (2000), 66–70.
31. Hua, Y., Sahashi, K., Rigo, F., Hung, G., Horev, G., Bennett, C.F., Krainer, A.R., Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature 478 (2011), 123–126.
32. Hunter, G., Aghamaleky Sarvestany, A., Roche, S.L., Symes, R.C., Gillingwater, T.H., SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy. Hum. Mol. Genet. 23 (2014), 2235–2250.
33. Hunter, G., Powis, R.A., Jones, R.A., Groen, E.J.N., Shorrock, H.K., Lane, F.M., Zheng, Y., Sherman, D.L., Brophy, P.J., Gillingwater, T.H., Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy. Hum. Mol. Genet. 25 (2016), 2853–2861.
34. Ingolia, N.T., Lareau, L.F., Weissman, J.S., Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147 (2011), 789–802.
35. Jablonka, S., Bandilla, M., Wiese, S., Bühler, D., Wirth, B., Sendtner, M., Fischer, U., Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Hum. Mol. Genet. 10 (2001), 497–505.
36. 3 assembly factors to propagate assembly of domains I and II of 25S rRNA in yeast 60S ribosomal subunits. RNA 18 (2012), 1805–1822.
37. Jung, H., Gkogkas, C.G., Sonenberg, N., Holt, C.E., Remote control of gene function by local translation. Cell 157 (2014), 26–40.
38. King, H.A., Gerber, A.P., Translatome profiling: methods for genome-scale analysis of mRNA translation. Brief. Funct. Genomics 15 (2016), 22–31.
39. Landowski, M., O'Donohue, M.-F., Buros, C., Ghazvinian, R., Montel-Lehry, N., Vlachos, A., Sieff, C.A., Newburger, P.E., Niewiadomska, E., Matysiak, M., et al. Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum. Genet. 132 (2013), 1265–1274.
40. Le, T.T., Pham, L.T., Butchbach, M.E.R., Zhang, H.L., Monani, U.R., Coovert, D.D., Gavrilina, T.O., Xing, L., Bassell, G.J., Burghes, A.H.M., SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum. Mol. Genet. 14 (2005), 845–857.
41. Lee, J., Hwang, Y.J., Boo, J.H., Han, D., Kwon, O.K., Todorova, K., Kowall, N.W., Kim, Y., Ryu, H., Dysregulation of upstream binding factor-1 acetylation at K352 is linked to impaired ribosomal DNA transcription in Huntington's disease. Cell Death Differ. 18 (2011), 1726–1735.
42. Lefebvre, S., Bürglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80 (1995), 155–165.
43. Liu-Yesucevitz, L., Bassell, G.J., Gitler, A.D., Hart, A.C., Klann, E., Richter, J.D., Warren, S.T., Wolozin, B., Local RNA translation at the synapse and in disease. J. Neurosci. 31 (2011), 16086–16093.
44. Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 (2001), 402–408.
45. Lo, K.-Y., Li, Z., Wang, F., Marcotte, E.M., Johnson, A.W., Ribosome stalk assembly requires the dual-specificity phosphatase Yvh1 for the exchange of Mrt4 with P0. J. Cell Biol. 186 (2009), 849–862.
46. Lorson, C.L., Hahnen, E., Androphy, E.J., Wirth, B., A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl. Acad. Sci. USA 96 (1999), 6307–6311.
47. Lunelli, L., Bernabò, P., Bolner, A., Vaghi, V., Marchioretto, M., Viero, G., Peering at Brain Polysomes with Atomic Force Microscopy. J. Vis. Exp., 109, 2016, e53851.
48. Lunn, M.R., Wang, C.H., Spinal muscular atrophy. Lancet 371 (2008), 2120–2133.
49. Ortiz, P.A., Kinzy, T.G., Dominant-negative mutant phenotypes and the regulation of translation elongation factor 2 levels in yeast. Nucleic Acids Res. 33 (2005), 5740–5748.
50. Passini, M.A., Bu, J., Roskelley, E.M., Richards, A.M., Sardi, S.P., O'Riordan, C.R., Klinger, K.W., Shihabuddin, L.S., Cheng, S.H., CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy. J. Clin. Invest. 120 (2010), 1253–1264.
51. Piazzon, N., Rage, F., Schlotter, F., Moine, H., Branlant, C., Massenet, S., In vitro and in cellulo evidences for association of the survival of motor neuron complex with the fragile X mental retardation protein. J. Biol. Chem. 283 (2008), 5598–5610.
52. Powis, R.A., Gillingwater, T.H., Selective loss of alpha motor neurons with sparing of gamma motor neurons and spinal cord cholinergic neurons in a mouse model of spinal muscular atrophy. J. Anat. 228 (2016), 443–451.
53. Renton, A.E., Chiò, A., Traynor, B.J., State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 17 (2014), 17–23.
54. Rossoll, W., Jablonka, S., Andreassi, C., Kröning, A.-K., Karle, K., Monani, U.R., Sendtner, M., Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J. Cell Biol. 163 (2003), 801–812.
55. Sanchez, G., Dury, A.Y., Murray, L.M., Biondi, O., Tadesse, H., El Fatimy, R., Kothary, R., Charbonnier, F., Khandjian, E.W., Côté, J., A novel function for the survival motoneuron protein as a translational regulator. Hum. Mol. Genet. 22 (2013), 668–684.
56. Santagata, S., Mendillo, M.L., Tang, Y. -c., Subramanian, A., Perley, C.C., Roche, S.P., Wong, B., Narayan, R., Kwon, H., Koeva, M., et al. Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science, 341, 2013, 1238303.
57. Sephton, C.F., Yu, G., The function of RNA-binding proteins at the synapse: implications for neurodegeneration. Cell. Mol. Life Sci. 72 (2015), 3621–3635.
58. Shababi, M., Habibi, J., Yang, H.T., Vale, S.M., Sewell, W.A., Lorson, C.L., Cardiac defects contribute to the pathology of spinal muscular atrophy models. Hum. Mol. Genet. 19 (2010), 4059–4071.
59. Shi, Z., Fujii, K., Kovary, K.M., Genuth, N.R., Röst, H.L., Teruel, M.N., Barna, M., Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide. Mol. Cell 67 (2017), 71–83.e7.
60. Shigeoka, T., Jung, H., Jung, J., Turner-Bridger, B., Ohk, J., Lin, J.Q., Amieux, P.S., Holt, C.E., Dynamic Axonal Translation in Developing and Mature Visual Circuits. Cell 166 (2016), 181–192.
61. Shpargel, K.B., Matera, A.G., Gemin proteins are required for efficient assembly of Sm-class ribonucleoproteins. Proc. Natl. Acad. Sci. USA 102 (2005), 17372–17377.
62. Sleigh, J.N., Gillingwater, T.H., Talbot, K., The contribution of mouse models to understanding the pathogenesis of spinal muscular atrophy. Dis. Model. Mech. 4 (2011), 457–467.
63. So, B.R., Wan, L., Zhang, Z., Li, P., Babiash, E., Duan, J., Younis, I., Dreyfuss, G., A U1 snRNP-specific assembly pathway reveals the SMN complex as a versatile hub for RNP exchange. Nat. Struct. Mol. Biol. 23 (2016), 225–230.
64. Somers, E., Lees, R.D., Hoban, K., Sleigh, J.N., Zhou, H., Muntoni, F., Talbot, K., Gillingwater, T.H., Parson, S.H., Vascular Defects and Spinal Cord Hypoxia in Spinal Muscular Atrophy. Ann. Neurol. 79 (2016), 217–230.
65. Tebaldi, T., Re, A., Viero, G., Pegoretti, I., Passerini, A., Blanzieri, E., Quattrone, A., Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells. BMC Genomics, 13, 2012, 220.
66. Tebaldi, T., Dassi, E., Kostoska, G., Viero, G., Quattrone, A., tRanslatome: an R/Bioconductor package to portray translational control. Bioinformatics 30 (2014), 289–291.
67. Tiedje, C., Ronkina, N., Tehrani, M., Dhamija, S., Laass, K., Holtmann, H., Kotlyarov, A., Gaestel, M., The p38/MK2-driven exchange between tristetraprolin and HuR regulates AU-rich element-dependent translation. PLoS Genet., 8, 2012, e1002977.
68. Tisdale, S., Pellizzoni, L., Disease mechanisms and therapeutic approaches in spinal muscular atrophy. J. Neurosci. 35 (2015), 8691–8700.
69. Tisdale, S., Lotti, F., Saieva, L., Van Meerbeke, J.P., Crawford, T.O., Sumner, C.J., Mentis, G.Z., Pellizzoni, L., SMN is essential for the biogenesis of U7 small nuclear ribonucleoprotein and 3′-end formation of histone mRNAs. Cell Rep. 5 (2013), 1187–1195.
70. Van Battum, E.Y., Gunput, R.A., Lemstra, S., Groen, E.J., Yu, K.L., Adolfs, Y., Zhou, Y., Hoogenraad, C.C., Yoshida, Y., Schachner, M., et al. The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections. Nat. Commun., 5, 2014, 4317.
71. Verheijen, M.H.G., Peviani, M., Hendricusdottir, R., Bell, E.M., Lammens, M., Smit, A.B., Bendotti, C., van Minnen, J., Increased axonal ribosome numbers is an early event in the pathogenesis of amyotrophic lateral sclerosis. PLoS ONE, 9, 2014, e87255.
72. Vilotti, S., Codrich, M., Dal Ferro, M., Pinto, M., Ferrer, I., Collavin, L., Gustincich, S., Zucchelli, S., Parkinson's disease DJ-1 L166P alters rRNA biogenesis by exclusion of TTRAP from the nucleolus and sequestration into cytoplasmic aggregates via TRAF6. PLoS ONE, 7, 2012, e35051.
73. Wehner, K.A., Ayala, L., Kim, Y., Young, P.J., Hosler, B.A., Lorson, C.L., Baserga, S.J., Francis, J.W., Survival motor neuron protein in the nucleolus of mammalian neurons. Brain Res. 945 (2002), 160–173.
74. Wessel, D., Flügge, U.I., A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal. Biochem. 138 (1984), 141–143.
75. Wishart, T.M., Huang, J.P.-W., Murray, L.M., Lamont, D.J., Mutsaers, C.A., Ross, J., Geldsetzer, P., Ansorge, O., Talbot, K., Parson, S.H., Gillingwater, T.H., SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy. Hum. Mol. Genet. 19 (2010), 4216–4228.
76. Wishart, T.M., Mutsaers, C.A., Riessland, M., Reimer, M.M., Hunter, G., Hannam, M.L., Eaton, S.L., Fuller, H.R., Roche, S.L., Somers, E., et al. Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy. J. Clin. Invest. 124 (2014), 1821–1834.
77. Xiao, Z., Zou, Q., Liu, Y., Yang, X., Genome-wide assessment of differential translations with ribosome profiling data. Nat. Commun., 7, 2016, 11194.
78. Zhang, Z., Lotti, F., Dittmar, K., Younis, I., Wan, L., Kasim, M., Dreyfuss, G., SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133 (2008), 585–600.
79. Zhou, H., Janghra, N., Mitrpant, C., Dickinson, R.L., Anthony, K., Price, L., Eperon, I.C., Wilton, S.D., Morgan, J., Muntoni, F., A novel morpholino oligomer targeting ISS-N1 improves rescue of severe spinal muscular atrophy transgenic mice. Hum. Gene Ther. 24 (2013), 331–342.