RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2

Neuron

Volumn 95, Issue 6, 2017, Pages 1292-1305.e5

  Zu, Tao ^a   Cleary, John D ^a   Liu, Yuanjing ^a   Bañez Coronel, Monica ^a   Bubenik, Jodi L ^a   Ayhan, Fatma ^a   Ashizawa, Tetsuo ^a,c   Xia, Guangbin ^a   Clark, H Brent ^d   Yachnis, Anthony T ^b   Swanson, Maurice S ^a   Ranum, Laura P W ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^c HOUSTON METHODIST HOSPITAL   (United States)

^d UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

C9ORF72; DM; DM2; MBNL; muscleblind proteins; myotonic dystrophy; non ATG translation; non AUG initiation; RAN translation; RNA foci

Indexed keywords

MUSCLEBLIND 1 PROTEIN; RAN PROTEIN; RNA; RNA BINDING PROTEIN; UNCLASSIFIED DRUG; CNBP PROTEIN, HUMAN; MBNL1 PROTEIN, HUMAN;

ARTICLE; ASTROCYTE; AUTOPSY; BIOACCUMULATION; BRAIN CORTEX; CLINICAL ARTICLE; CONTROLLED STUDY; CORPUS STRIATUM; CYTOPLASM; EMBRYO; GAIN OF FUNCTION MUTATION; GENETIC TRANSCRIPTION; GLIA; GRAY MATTER; HIPPOCAMPUS; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; MACROPHAGE; MYOTONIC DYSTROPHY; NERVE CELL; NUCLEOTIDE REPEAT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA TRANSLATION; TRANSLATION REGULATION; WHITE MATTER; BIOSYNTHESIS; BRAIN; CELL CULTURE; CELL SURVIVAL; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MUTATION; PROTEIN SYNTHESIS;

BRAIN; CELL SURVIVAL; CELLS, CULTURED; GENE EXPRESSION REGULATION; HUMANS; MUTATION; MYOTONIC DYSTROPHY; PROTEIN BIOSYNTHESIS; RAN GTP-BINDING PROTEIN; RNA; RNA-BINDING PROTEINS;

EID: 85030615756     PISSN: 08966273     EISSN: 10974199     Source Type: Journal    
DOI: 10.1016/j.neuron.2017.08.039     Document Type: Article

References (53)

1. Ash, P.E., Bieniek, K.F., Gendron, T.F., Caulfield, T., Lin, W.L., Dejesus-Hernandez, M., van Blitterswijk, M.M., Jansen-West, K., Paul, J.W. 3rd, Rademakers, R., et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77 (2013), 639–646.
2. Bañez-Coronel, M., Ayhan, F., Tarabochia, A.D., Zu, T., Perez, B.A., Tusi, S.K., Pletnikova, O., Borchelt, D.R., Ross, C.A., Margolis, R.L., et al. RAN translation in Huntington disease. Neuron 88 (2015), 667–677.
3. Björkqvist, M., Wild, E.J., Thiele, J., Silvestroni, A., Andre, R., Lahiri, N., Raibon, E., Lee, R.V., Benn, C.L., Soulet, D., et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J. Exp. Med. 205 (2008), 1869–1877.
4. Brook, J.D., McCurrach, M.E., Harley, H.G., Buckler, A.J., Church, D., Aburatani, H., Hunter, K., Stanton, V.P., Thirion, J.-P., Hudson, T., et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68 (1992), 799–808.
5. Charizanis, K., Lee, K.Y., Batra, R., Goodwin, M., Zhang, C., Yuan, Y., Shiue, L., Cline, M., Scotti, M.M., Xia, G., et al. Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy. Neuron 75 (2012), 437–450.
6. Cho, D.H., Thienes, C.P., Mahoney, S.E., Analau, E., Filippova, G.N., Tapscott, S.J., Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF. Mol. Cell 20 (2005), 483–489.
7. Cleary, J.D., Ranum, L.P., Repeat associated non-ATG (RAN) translation: new starts in microsatellite expansion disorders. Curr. Opin. Genet. Dev. 26 (2014), 6–15.
8. Cleary, J.D., Ranum, L.P., New developments in RAN translation: insights from multiple diseases. Curr. Opin. Genet. Dev. 44 (2017), 125–134.
9. Conforti, R., de Cristofaro, M., Cristofano, A., Brogna, B., Sardaro, A., Tedeschi, G., Cirillo, S., Di Costanzo, A., Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: a longitudinal case series study. Neuroradiol. J. 29 (2016), 36–45.
10. Fu, Y.-H., Pizzuti, A., Fenwick, R.G.J. Jr., King, J., Rajnarayan, S., Dunne, P.W., Dubel, J., Nasser, G.A., Ashizawa, T., de Jong, P., et al. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255 (1992), 1256–1258.
11. Gagnon, K.T., Li, L., Janowski, B.A., Corey, D.R., Analysis of nuclear RNA interference in human cells by subcellular fractionation and Argonaute loading. Nat. Protoc. 9 (2014), 2045–2060.
12. Goodwin, M., Mohan, A., Batra, R., Lee, K.Y., Charizanis, K., Fernández Gómez, F.J., Eddarkaoui, S., Sergeant, N., Buée, L., Kimura, T., et al. MBNL sequestration by toxic RNAs and RNA misprocessing in the myotonic dystrophy brain. Cell Rep. 12 (2015), 1159–1168.
13. Harper, P.S., Myotonic Dystrophy. Second Edition, 1989, W.B. Saunders.
14. Ho, T.H., Savkur, R.S., Poulos, M.G., Mancini, M.A., Swanson, M.S., Cooper, T.A., Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy. J. Cell Sci. 118 (2005), 2923–2933.
15. Ishiguro, T., Sato, N., Ueyama, M., Fujikake, N., Sellier, C., Kanegami, A., Tokuda, E., Zamiri, B., Gall-Duncan, T., Mirceta, M., et al. Regulatory role of RNA chaperone TDP-43 for RNA misfolding and repeat-associated translation in SCA31. Neuron 94 (2017), 108–124.e7.
16. Kanadia, R.N., Urbinati, C.R., Crusselle, V.J., Luo, D., Lee, Y.J., Harrison, J.K., Oh, S.P., Swanson, M.S., Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3. Gene Expr. Patterns 3 (2003), 459–462.
17. Katayama, S., Tomaru, Y., Kasukawa, T., Waki, K., Nakanishi, M., Nakamura, M., Nishida, H., Yap, C.C., Suzuki, M., Kawai, J., et al. RIKEN Genome Exploration Research Group Genome Science Group (Genome Network Project Core Group), FANTOM Consortium. Antisense transcription in the mammalian transcriptome. Science 309 (2005), 1564–1566.
18. Kino, Y., Mori, D., Oma, Y., Takeshita, Y., Sasagawa, N., Ishiura, S., Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats. Hum. Mol. Genet. 13 (2004), 495–507.
19. Kobayashi, H., Abe, K., Matsuura, T., Ikeda, Y., Hitomi, T., Akechi, Y., Habu, T., Liu, W., Okuda, H., Koizumi, A., Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am. J. Hum. Genet. 89 (2011), 121–130.
20. Krans, A., Kearse, M.G., Todd, P.K., Repeat-associated non-AUG translation from antisense CCG repeats in fragile X tremor/ataxia syndrome. Ann. Neurol. 80 (2016), 871–881.
21. Kwon, I., Xiang, S., Kato, M., Wu, L., Theodoropoulos, P., Wang, T., Kim, J., Yun, J., Xie, Y., McKnight, S.L., Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells. Science 345 (2014), 1139–1145.
22. Ladd, P.D., Smith, L.E., Rabaia, N.A., Moore, J.M., Georges, S.A., Hansen, R.S., Hagerman, R.J., Tassone, F., Tapscott, S.J., Filippova, G.N., An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals. Hum. Mol. Genet. 16 (2007), 3174–3187.
23. Lee, K.Y., Li, M., Manchanda, M., Batra, R., Charizanis, K., Mohan, A., Warren, S.A., Chamberlain, C.M., Finn, D., Hong, H., et al. Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Mol. Med. 5 (2013), 1887–1900.
24. Libby, R.T., Hagerman, K.A., Pineda, V.V., Lau, R., Cho, D.H., Baccam, S.L., Axford, M.M., Cleary, J.D., Moore, J.M., Sopher, B.L., et al. CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination. PLoS Genet., 4, 2008, e1000257.
25. Liquori, C.L., Ricker, K., Moseley, M.L., Jacobsen, J.F., Kress, W., Naylor, S.L., Day, J.W., Ranum, L.P., Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 293 (2001), 864–867.
26. Mahadevan, M., Tsilfidis, C., Sabourin, L., Shutler, G., Amemiya, C., Jansen, G., Neville, C., Narang, M., Barceló J., O'Hoy, K., et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255 (1992), 1253–1255.
27. Mankodi, A., Urbinati, C.R., Yuan, Q.P., Moxley, R.T., Sansone, V., Krym, M., Henderson, D., Schalling, M., Swanson, M.S., Thornton, C.A., Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2. Hum. Mol. Genet. 10 (2001), 2165–2170.
28. Meola, G., Myotonic dystrophies as a brain disorder. Neurol. Sci. 31 (2010), 863–864.
29. Miller, J.W., Urbinati, C.R., Teng-Umnuay, P., Stenberg, M.G., Byrne, B.J., Thornton, C.A., Swanson, M.S., Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J. 19 (2000), 4439–4448.
30. Minnerop, M., Weber, B., Schoene-Bake, J.C., Roeske, S., Mirbach, S., Anspach, C., Schneider-Gold, C., Betz, R.C., Helmstaedter, C., Tittgemeyer, M., et al. The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease. Brain 134 (2011), 3530–3546.
31. Mizielinska, S., Gronke, S., Niccoli, T., Ridler, C.E., Clayton, E.L., Devoy, A., Moens, T., Norona, F.E., Woollacott, I.O.C., Pietrzyk, J., et al. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science 345 (2014), 1192–1194.
32. Mori, K., Weng, S.M., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., Schmid, B., Kretzschmar, H.A., Cruts, M., Van Broeckhoven, C., et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339 (2013), 1335–1338.
33. Moseley, M.L., Zu, T., Ikeda, Y., Gao, W., Mosemiller, A.K., Daughters, R.S., Chen, G., Weatherspoon, M.R., Clark, H.B., Ebner, T.J., et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat. Genet. 38 (2006), 758–769.
34. Mykowska, A., Sobczak, K., Wojciechowska, M., Kozlowski, P., Krzyzosiak, W.J., CAG repeats mimic CUG repeats in the misregulation of alternative splicing. Nucleic Acids Res. 39 (2011), 8938–8951.
35. Nelson, D.L., Orr, H.T., Warren, S.T., The unstable repeats—three evolving faces of neurological disease. Neuron 77 (2013), 825–843.
36. Ogata, A., Terae, S., Fujita, M., Tashiro, K., Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study. Neuroradiology 40 (1998), 411–415.
37. Ranum, L.P., Cooper, T.A., RNA-mediated neuromuscular disorders. Annu. Rev. Neurosci. 29 (2006), 259–277.
38. Savkur, R.S., Philips, A.V., Cooper, T.A., Dalton, J.C., Moseley, M.L., Ranum, L.P., Day, J.W., Insulin receptor splicing alteration in myotonic dystrophy type 2. Am. J. Hum. Genet. 74 (2004), 1309–1313.
39. Scotti, M.M., Swanson, M.S., RNA mis-splicing in disease. Nat. Rev. Genet. 17 (2016), 19–32.
40. Shulman, J.M., De Jager, P.L., Feany, M.B., Parkinson's disease: genetics and pathogenesis. Annu. Rev. Pathol. 6 (2011), 193–222.
41. Sun, X., Li, P.P., Zhu, S., Cohen, R., Marque, L.O., Ross, C.A., Pulst, S.M., Chan, H.Y., Margolis, R.L., Rudnicki, D.D., Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65. Sci. Rep., 5, 2015, 12521.
42. Todd, P.K., Oh, S.Y., Krans, A., He, F., Sellier, C., Frazer, M., Renoux, A.J., Chen, K.C., Scaglione, K.M., Basrur, V., et al. CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron 78 (2013), 440–455.
43. Vonsattel, J.P., Keller, C., Cortes Ramirez, E.P., Huntington's disease—neuropathology. Handb. Clin. Neurol. 100 (2011), 83–100.
44. Wagner, S.D., Struck, A.J., Gupta, R., Farnsworth, D.R., Mahady, A.E., Eichinger, K., Thornton, C.A., Wang, E.T., Berglund, J.A., Dose-dependent regulation of alternative splicing by MBNL proteins reveals biomarkers for myotonic dystrophy. PLoS Genet., 12, 2016, e1006316.
45. Wang, E.T., Cody, N.A., Jog, S., Biancolella, M., Wang, T.T., Treacy, D.J., Luo, S., Schroth, G.P., Housman, D.E., Reddy, S., et al. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell 150 (2012), 710–724.
46. Wozniak, J.R., Mueller, B.A., Ward, E.E., Lim, K.O., Day, J.W., White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study. Neuromuscul. Disord. 21 (2011), 89–96.
47. Wozniak, J.R., Mueller, B.A., Bell, C.J., Muetzel, R.L., Lim, K.O., Day, J.W., Diffusion tensor imaging reveals widespread white matter abnormalities in children and adolescents with myotonic dystrophy type 1. J. Neurol. 260 (2013), 1122–1131.
48. Wozniak, J.R., Mueller, B.A., Lim, K.O., Hemmy, L.S., Day, J.W., Tractography reveals diffuse white matter abnormalities in myotonic dystrophy type 1. J. Neurol. Sci. 341 (2014), 73–78.
49. Yuan, Y., Compton, S.A., Sobczak, K., Stenberg, M.G., Thornton, C.A., Griffith, J.D., Swanson, M.S., Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Res. 35 (2007), 5474–5486.
50. Zanigni, S., Evangelisti, S., Giannoccaro, M.P., Oppi, F., Poda, R., Giorgio, A., Testa, C., Manners, D.N., Avoni, P., Gramegna, L.L., et al. Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1. Neuroimage Clin. 11 (2016), 678–685.
51. Zhang, Y., Chen, K., Sloan, S.A., Bennett, M.L., Scholze, A.R., O'Keeffe, S., Phatnani, H.P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34 (2014), 11929–11947.
52. Zu, T., Gibbens, B., Doty, N.S., Gomes-Pereira, M., Huguet, A., Stone, M.D., Margolis, J., Peterson, M., Markowski, T.W., Ingram, M.A., et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc. Natl. Acad. Sci. USA 108 (2011), 260–265.
53. Zu, T., Liu, Y., Bañez-Coronel, M., Reid, T., Pletnikova, O., Lewis, J., Miller, T.M., Harms, M.B., Falchook, A.E., Subramony, S.H., et al. RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proc. Natl. Acad. Sci. USA 110 (2013), E4968–E4977.