Mislocalised FUS mutants stall spliceosomal snRNPs in the cytoplasm

Neurobiology of Disease

Volumn 55, Issue , 2013, Pages 120-128

  Gerbino, Valeria ^a,b   Carrì, Maria Teresa ^a,b   Cozzolino, Mauro ^a,c   Achsel, Tilmann ^d  

^a IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c INSTITUTE OF TRANSLATIONAL PHARMACOLOGY   (Italy)

^d DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

Author keywords

Amyotrophic lateral sclerosis; Fused in Sarcoma Protein (FUS); Small nuclear RNA; Spinal muscular atrophy; Survival of Motor Neuron Protein (SMN)

Indexed keywords

FUSED IN SARCOMA PROTEIN; SMALL NUCLEAR RIBONUCLEOPROTEIN; SURVIVAL MOTOR NEURON PROTEIN;

ALTERNATIVE RNA SPLICING; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CYTOPLASM; FLUORESCENCE IN SITU HYBRIDIZATION; GENETIC TRANSFECTION; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; MOUSE; MUTANT; MUTATION; NERVE CELL; NONHUMAN; PLASMID; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEPLETION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPINAL MUSCULAR ATROPHY;

ANIMALS; CELL LINE, TRANSFORMED; CYTOPLASM; HUMANS; IMMUNOPRECIPITATION; MICE; MOTOR NEURONS; MUTATION; RIBONUCLEOPROTEINS, SMALL NUCLEAR; RNA-BINDING PROTEIN FUS; SPLICEOSOMES; SURVIVAL OF MOTOR NEURON 1 PROTEIN; TRANSFECTION;

EID: 84877590417     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2013.03.003     Document Type: Article

References (38)

1. Arnold E.S., Ling S.C., et al. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc. Natl. Acad. Sci. U. S. A. 2013, 110(8):E736-E745.
2. Bäumer D., Lee S., et al. Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genet. 2009, 5(12):e1000773.
3. Bäumer D., Ansorge O., et al. The role of RNA processing in the pathogenesis of motor neuron degeneration. Expert Rev. Mol. Med. 2010, 12:e21.
4. Boulisfane N., Choleza M., et al. Impaired minor tri-snRNP assembly generates differential splicing defects of U12-type introns in lymphoblasts derived from a type I SMA patient. Hum. Mol. Genet. 2011, 20(4):641-648.
5. Brahms H., Raker V.A., et al. A major, novel systemic lupus erythematosus autoantibody class recognizes the E, F, and G Sm snRNP proteins as an E-F-G complex but not in their denatured states. Arthritis Rheum. 1997, 40(4):672-682.
6. Burghes A.H., Beattie C.E. Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?. Nat. Rev. Neurosci. 2009, 10(8):597-609.
7. Carvalho T., Almeida F., et al. The spinal muscular atrophy disease gene product, SMN: a link between snRNP biogenesis and the Cajal (coiled) body. J. Cell Biol. 1999, 147(4):715-728.
8. Chari A., Paknia E., et al. The role of RNP biogenesis in spinal muscular atrophy. Curr. Opin. Cell Biol. 2009, 21(3):387-393.
9. Chiò A., Restagno G., et al. Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation. Neurobiol. Aging 2009, 30(8):1272-1275.
10. Cozzolino M., Pesaresi M.G., et al. Amyotrophic lateral sclerosis: new insights into underlying molecular mechanisms and opportunities for therapeutic intervention. Antioxid. Redox Signal. 2012, 17(9):1277-1330.
11. Dormann D., Haass C. TDP-43 and FUS: a nuclear affair. Trends Neurosci. 2011, 34(7):339-348.
12. Dormann D., Madl T., et al. Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. EMBO J. 2012, 31(22):4258-4275.
13. Dormann D., Rodde R., et al. ALS-associated fused in sarcoma (FUS) mutations disrupt transportin-mediated nuclear import. EMBO J. 2010, 29(16):2841-2857.
14. Drepper C., Herrmann T., et al. C-terminal FUS/TLS mutations in familial and sporadic ALS in Germany. Neurobiol. Aging 2011, 32(3):548.e1-548.e4.
15. Ferri A., Cozzolino M., et al. Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials. Proc. Natl. Acad. Sci. U.S.A. 2006, 103(37):13860-13865.
16. Gabanella F., Butchbach M.E., et al. Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One 2007, 2(9):e921.
17. Gal J., Zhang J., et al. Nuclear localization sequence of FUS and induction of stress granules by ALS mutants. Neurobiol. Aging 2011, 32(12):2323.e2327-2323.e2340.
18. Hackl W., Lührmann R. Molecular cloning and subcellular localisation of the snRNP-associated protein 69KD, a structural homologue of the proto-oncoproteins TLS and EWS with RNA and DNA-binding properties. J. Mol. Biol. 1996, 264(5):843-851.
19. Hackl W., Fischer U., et al. A 69-kD protein that associates reversibly with the Sm core domain of several spliceosomal snRNP species. J. Cell Biol. 1994, 124(3):261-272.
20. Hofmann Y., Lorson C.L., et al. Htra2-beta 1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 (SMN2). Proc. Natl. Acad. Sci. U.S.A. 2000, 97(17):9618-9623.
21. Jobert L., Pinzón N., et al. Human U1 snRNA forms a new chromatin-associated snRNP with TAF15. EMBO Rep. 2009, 10(5):494-500.
22. Kwiatkowski T.J., Bosco D.A., et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323(5918):1205-1208.
23. Lagier-Tourenne C., Cleveland D.W. Rethinking ALS: the FUS about TDP-43. Cell 2009, 136(6):1001-1004.
24. Lagier-Tourenne C., Polymenidou M., et al. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat. Neurosci. 2012, 15(11):1488-1497.
25. Lagier-Tourenne C., Polymenidou M., et al. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet. 2012, 19(R1):R46-R64.
26. Lenzken S.C., Romeo V., et al. Mutant SOD1 and mitochondrial damage alter expression and splicing of genes controlling neuritogenesis in models of neurodegeneration. Hum. Mutat. 2011, 32(2):168-182.
27. Lotti F., Imlach W.L., et al. An SMN-dependent U12 splicing event essential for motor circuit function. Cell 2012, 151(2):440-454.
28. Maracchioni A., Totaro A., et al. Mitochondrial damage modulates alternative splicing in neuronal cells: implications for neurodegeneration. J. Neurochem. 2007, 100(1):142-153.
29. Mitchell J.C., McGoldrick P., et al. Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol. 2013, 125(2):273-288.
30. Narayanan U., Achsel T., et al. Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein. Mol. Cell 2004, 16(2):223-234.
31. Ranum L.P., Cooper T.A. RNA-mediated neuromuscular disorders. Annu. Rev. Neurosci. 2006, 29:259-277.
32. Schaffert N., Hossbach M., et al. RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal bodies. EMBO J. 2004, 23(15):3000-3009.
33. Stanek D., Neugebauer K.M. Detection of snRNP assembly intermediates in Cajal bodies by fluorescence resonance energy transfer. J. Cell Biol. 2004, 166(7):1015-1025.
34. Vance C., Rogelj B., et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323(5918):1208-1211.
35. Will C.L., Lührmann R. Spliceosomal UsnRNP biogenesis, structure and function. Curr. Opin. Cell Biol. 2001, 13(3):290-301.
36. Yamazaki T., Chen S., et al. FUS-SMN protein interactions link the motor neuron diseases ALS and SMA. Cell Rep. 2012, 2(4):799-806.
37. Yan J., Deng H.X., et al. Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia. Neurology 2010, 75(9):807-814.
38. Zhang Z., Lotti F., et al. SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 2008, 133(4):585-600.