A novel fragile X syndrome mutation reveals a conserved role for the carboxy-terminus in FMRP localization and function

EMBO Molecular Medicine

Volumn 7, Issue 4, 2015, Pages 423-437

  Okray, Zeynep ^a,b   de Esch, Celine E F ^c   Van Esch, Hilde ^b   Devriendt, Koen ^b   Claeys, Annelies ^a,b   Yan, Jiekun ^a,b   Verbeeck, Jelle ^a,b   Froyen, Guy ^a,b   Willemsen, Rob ^c   de Vrij, Femke M S ^c   Hassan, Bassem A ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Drosophila; Axon guidance; Fragile X syndrome; Nuclear export; Nucleolus

Indexed keywords

FRAGILE X MENTAL RETARDATION PROTEIN; GENOMIC DNA; MESSENGER RNA; NUCLEOPHOSMIN; FMR1 PROTEIN, HUMAN; NUCLEAR LOCALIZATION SIGNAL;

ADULT; AMINO ACID SEQUENCE; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELLULAR DISTRIBUTION; CLINICAL ARTICLE; CONTROLLED STUDY; DROSOPHILA MELANOGASTER; EMBRYO; EXON; FMR1 GENE; FRAGILE X SYNDROME; FRAMESHIFT MUTATION; GENE; GENE EXPRESSION; GENE FUNCTION; GENE LOCATION; GENE LOCUS; GENETIC SCREENING; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VIVO STUDY; INTELLIGENCE QUOTIENT; LOSS OF FUNCTION MUTATION; LYMPHOBLASTOID CELL LINE; MALE; MOLECULAR MEDICINE; MOUSE; NERVE CELL; NEUROBLASTOMA; NONHUMAN; NONSENSE MEDIATED MRNA DECAY; NUCLEAR LOCALIZATION SIGNAL; OPEN READING FRAME; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN FAMILY; SOCIAL INTERACTION; STOP CODON; UNTRANSLATED REGION; WESTERN BLOTTING; ANIMAL; CELL NUCLEUS; GENETICS; METABOLISM; MUTATION; PATHOLOGY; PROTEIN TERTIARY STRUCTURE; PROTEIN TRANSPORT; TRANSFORMED CELL LINE; TRINUCLEOTIDE REPEAT; TUMOR CELL LINE;

ANIMALS; CELL LINE, TRANSFORMED; CELL LINE, TUMOR; CELL NUCLEUS; DROSOPHILA MELANOGASTER; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; MALE; MICE; MUTATION; NUCLEAR LOCALIZATION SIGNALS; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 84926203826     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.15252/emmm.201404576     Document Type: Article

References (62)

1. Ayaz D, Leyssen M, Koch M, Yan J, Srahna M, Sheeba V, Fogle KJ, Holmes TC, Hassan BA (2008) Axonal injury and regeneration in the adult brain of Drosophila. J Neurosci 28: 6010-6021
2. Bagni C, Greenough WT (2005) From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat Rev Neurosci 6: 376-387
3. Bakker CE, de Diego Otero Y, Bontekoe C, Raghoe P, Luteijn T, Hoogeveen AT, Oostra BA, Willemsen R (2000) Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse. Exp Cell Res 258: 162-170
4. Bassell GJ, Warren ST (2008) Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60: 201-214
5. Belser RC, Sudhalter V (2001) Conversational characteristics of children with fragile X syndrome: repetitive speech. Am J Ment Retard 106: 28-38
6. Berry-Kravis E (2002) Epilepsy in fragile X syndrome. Dev Med Child Neurol 44: 724-728
7. Blackwell E, Zhang X, Ceman S (2010) Arginines of the RGG box regulate FMRP association with polyribosomes and mRNA. Hum Mol Genet 19: 1314-1323
8. Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401-415
9. de Castro E, Sigrist CJ, Gattiker A, Bulliard V, Langendijk-Genevaux PS, Gasteiger E, Bairoch A, Hulo N (2006) ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Res 34: W362-W365
10. Coffee B, Ikeda M, Budimirovic DB, Hjelm LN, Kaufmann WE, Warren ST (2008) Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis: a case report and review of the literature. Am J Med Genet A 146A: 1358-1367
11. Collins SC, Bray SM, Suhl JA, Cutler DJ, Coffee B, Zwick ME, Warren ST (2010a) Identification of novel FMR1 variants by massively parallel sequencing in developmentally delayed males. Am J Med Genet A 152A: 2512-2520
12. Collins SC, Coffee B, Benke PJ, Berry-Kravis E, Gilbert F, Oostra B, Halley D, Zwick ME, Cutler DJ, Warren ST (2010b) Array-based FMR1 sequencing and deletion analysis in patients with a fragile X syndrome-like phenotype. PLoS ONE 5: e9476
13. Cornish K, Sudhalter V, Turk J (2004) Attention and language in fragile X. Ment Retard Dev Disabil Res Rev 10: 11-16
14. Crowe SF, Hay DA (1990) Neuropsychological dimensions of the fragile X syndrome: support for a non-dominant hemisphere dysfunction hypothesis. Neuropsychologia 28: 9-16
15. Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB (2001) Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107: 489-499
16. De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, Van den Bos F, de Graaff E, Oostra BA, Willems PJ (1993) A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 3: 31-35
17. Devys D, Lutz Y, Rouyer N, Bellocq JP, Mandel JL (1993) The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet 4: 335-340
18. Dury AY, El Fatimy R, Tremblay S, Rose TM, Cote J, De Koninck P, Khandjian EW (2013) Nuclear fragile X mental retardation protein is localized to cajal bodies. PLoS Genet 9: e1003890
19. Feng Y, Absher D, Eberhart DE, Brown V, Malter HE, Warren ST (1997) FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Mol Cell 1: 109-118
20. Fernandez E, Rajan N, Bagni C (2013) The FMRP regulon: from targets to disease convergence. Front Neurosci 7: 191
21. Fisch GS, Simensen RJ, Schroer RJ (2002) Longitudinal changes in cognitive and adaptive behavior scores in children and adolescents with the fragile X mutation or autism. J Autism Dev Disord 32: 107-114
22. Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJ, Holden JJ, Fenwick RG Jr, Warren ST et al (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67: 1047-1058
23. Gedeon AK, Baker E, Robinson H, Partington MW, Gross B, Manca A, Korn B, Poustka A, Yu S, Sutherland GR et al (1992) Fragile X syndrome without CCG amplification has an FMR1 deletion. Nat Genet 1: 341-344
24. Gronskov K, Brondum-Nielsen K, Dedic A, Hjalgrim H (2011) A nonsense mutation in FMR1 causing fragile X syndrome. Eur J Hum Genet 19: 489-491
25. Hagerman RJ, Hull CE, Safanda JF, Carpenter I, Staley LW, O'Connor RA, Seydel C, Mazzocco MM, Snow K, Thibodeau SN et al (1994) High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet 51: 298-308
26. Kim M, Bellini M, Ceman S (2009) Fragile X mental retardation protein FMRP binds mRNAs in the nucleus. Mol Cell Biol 29: 214-228
27. Kirkpatrick LL, McIlwain KA, Nelson DL (2001) Comparative genomic sequence analysis of the FXR gene family: FMR1, FXR1, and FXR2. Genomics 78: 169-177
28. Kronk R, Bishop EE, Raspa M, Bickel JO, Mandel DA, Bailey DB Jr (2010) Prevalence, nature, and correlates of sleep problems among children with fragile X syndrome based on a large scale parent survey. Sleep 33: 679-687
29. Lachiewicz AM, Dawson DV (1994) Behavior problems of young girls with fragile X syndrome: factor scores on the Conners' Parent's questionnaire. Am J Med Genet 51: 364-369
30. Lachiewicz AM, Spiridigliozzi GA, Gullion CM, Ransford SN, Rao K (1994) Aberrant behaviors of young boys with fragile X syndrome. Am J Ment Retard 98: 567-579
31. Laggerbauer B, Ostareck D, Keidel EM, Ostareck-Lederer A, Fischer U (2001) Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum Mol Genet 10: 329-338
32. Levenga J, Buijsen RA, Rife M, Moine H, Nelson DL, Oostra BA, Willemsen R, de Vrij FM (2009) Ultrastructural analysis of the functional domains in FMRP using primary hippocampal mouse neurons. Neurobiol Dis 35: 241-250
33. Loesch DZ, Huggins RM, Hagerman RJ (2004) Phenotypic variation and FMRP levels in fragile X. Ment Retard Dev Disabil Res Rev 10: 31-41
34. Lugenbeel KA, Peier AM, Carson NL, Chudley AE, Nelson DL (1995) Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. Nat Genet 10: 483-485
35. McBride SM, Bell AJ, Jongens TA (2012) Behavior in a Drosophila model of fragile X. Results Probl Cell Differ 54: 83-117
36. Morales J, Hiesinger PR, Schroeder AJ, Kume K, Verstreken P, Jackson FR, Nelson DL, Hassan BA (2002) Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron 34: 961-972
37. Oberle I, Rousseau F, Heitz D, Kretz C, Devys D, Hanauer A, Boue J, Bertheas MF, Mandel JL (1991) Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252: 1097-1102
38. Okray Z, Hassan BA (2013) Genetic approaches in Drosophila for the study neurodevelopmental disorders. Neuropharmacology 68: 150-156
39. Pan L, Zhang YQ, Woodruff E, Broadie K (2004) The Drosophila fragile X gene negatively regulates neuronal elaboration and synaptic differentiation. Curr Biol 14: 1863-1870
40. Penagarikano O, Mulle JG, Warren ST (2007) The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 8: 109-129
41. Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, Nelson DL (1991) Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66: 817-822
42. Ramos A, Hollingworth D, Pastore A (2003) G-quartet-dependent recognition between the FMRP RGG box and RNA. RNA 9: 1198-1207
43. Reeve SP, Bassetto L, Genova GK, Kleyner Y, Leyssen M, Jackson FR, Hassan BA (2005) The Drosophila fragile X mental retardation protein controls actin dynamics by directly regulating profilin in the brain. Curr Biol 15: 1156-1163
44. Reeve SP, Lin X, Sahin BH, Jiang F, Yao A, Liu Z, Zhi H, Broadie K, Li W, Giangrande A et al (2008) Mutational analysis establishes a critical role for the N terminus of fragile X mental retardation protein FMRP. J Neurosci 28: 3221-3226
45. Rousseau F, Heitz D, Tarleton J, MacPherson J, Malmgren H, Dahl N, Barnicoat A, Mathew C, Mornet E, Tejada I et al (1994) A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2, 253 cases. Am J Hum Genet 55: 225-237
46. Schrier M, Severijnen LA, Reis S, Rife M, van't Padje S, van Cappellen G, Oostra BA, Willemsen R (2004) Transport kinetics of FMRP containing the I304N mutation of severe fragile X syndrome in neurites of living rat PC12 cells. Exp Neurol 189: 343-353
47. Siomi H, Choi M, Siomi MC, Nussbaum RL, Dreyfuss G (1994) Essential role for KH domains in RNA binding: impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. Cell 77: 33-39
48. Siomi MC, Siomi H, Sauer WH, Srinivasan S, Nussbaum RL, Dreyfuss G (1995) FXR1, an autosomal homolog of the fragile X mental retardation gene. EMBO J 14: 2401-2408
49. Soldano A, Okray Z, Janovska P, Tmejova K, Reynaud E, Claeys A, Yan J, Atak ZK, De Strooper B, Dura JM et al (2013) The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling. PLoS Biol 11: e1001562
50. Taha MS, Nouri K, Milroy LG, Moll JM, Herrmann C, Brunsveld L, Piekorz RP, Ahmadian MR (2014) Subcellular fractionation and localization studies reveal a direct interaction of the fragile X mental retardation protein (FMRP) with nucleolin. PLoS ONE 9: e91465
51. Tamanini F, Bontekoe C, Bakker CE, van Unen L, Anar B, Willemsen R, Yoshida M, Galjaard H, Oostra BA, Hoogeveen AT (1999) Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations. Hum Mol Genet 8: 863-869
52. Tamanini F, Kirkpatrick LL, Schonkeren J, van Unen L, Bontekoe C, Bakker C, Nelson DL, Galjaard H, Oostra BA, Hoogeveen AT (2000) The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins. Hum Mol Genet 9: 1487-1493
53. Tarleton J, Richie R, Schwartz C, Rao K, Aylsworth AS, Lachiewicz A (1993) An extensive de novo deletion removing FMR1 in a patient with mental retardation and the fragile X syndrome phenotype. Hum Mol Genet 2: 1973-1974
54. Venken KJ, He Y, Hoskins RA, Bellen HJ (2006) P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314: 1747-1751
55. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65: 905-914
56. de Vrij FM, Levenga J, van der Linde HC, Koekkoek SK, De Zeeuw CI, Nelson DL, Oostra BA, Willemsen R (2008) Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis 31: 127-132
57. Wan L, Dockendorff TC, Jongens TA, Dreyfuss G (2000) Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. Mol Cell Biol 20: 8536-8547
58. Willemsen R, Bontekoe C, Tamanini F, Galjaard H, Hoogeveen A, Oostra B (1996) Association of FMRP with ribosomal precursor particles in the nucleolus. Biochem Biophys Res Commun 225: 27-33
59. Wohrle D, Kotzot D, Hirst MC, Manca A, Korn B, Schmidt A, Barbi G, Rott HD, Poustka A, Davies KE et al (1992) A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome. Am J Hum Genet 51: 299-306
60. Wolff B, Sanglier JJ, Wang Y (1997) Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem Biol 4: 139-147
61. Zhang Y, O'Connor JP, Siomi MC, Srinivasan S, Dutra A, Nussbaum RL, Dreyfuss G (1995) The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J 14: 5358-5366
62. Zhang YQ, Bailey AM, Matthies HJ, Renden RB, Smith MA, Speese SD, Rubin GM, Broadie K (2001) Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107: 591-603