The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking in


The conserved NineTeen protein complex (NTC) is an integral subunit of the spliceosome and required for intron removal during pre-mRNA splicing. The complex associates with the spliceosome and participates in the regulation of conformational changes of core spliceosomal components, stabilizing RNA-RNA- as well as RNA-protein interactions. In addition, the NTC is involved in cell cycle checkpoint control, response to DNA damage, as well as formation and export of mRNP-particles. We have identified the Num1 protein as the homologue of SPF27, one of NTC core components, in the basidiomycetous fungus Ustilago maydis. Num1 is required for polarized growth of the fungal hyphae, and, in line with the described NTC functions, the num1 mutation affects the cell cycle and cell division. The num1 deletion influences splicing in U. maydis on a global scale, as RNA-Seq analysis revealed increased intron retention rates. Surprisingly, we identified in a screen for Num1 interacting proteins not only NTC core components as Prp19 and Cef1, but several proteins with putative functions during vesicle-mediated transport processes. Among others, Num1 interacts with the motor protein Kin1 in the cytoplasm. Similar phenotypes with respect to filamentous and polar growth, vacuolar morphology, as well as the motility of early endosomes corroborate the genetic interaction between Num1 and Kin1. Our data implicate a previously unidentified connection between a component of the splicing machinery and cytoplasmic transport processes. As the num1 deletion also affects cytoplasmic mRNA transport, the protein may constitute a novel functional interconnection between the two disparate processes of splicing and trafficking.


Vyšlo v časopise: The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking in. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004046
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004046

Souhrn

The conserved NineTeen protein complex (NTC) is an integral subunit of the spliceosome and required for intron removal during pre-mRNA splicing. The complex associates with the spliceosome and participates in the regulation of conformational changes of core spliceosomal components, stabilizing RNA-RNA- as well as RNA-protein interactions. In addition, the NTC is involved in cell cycle checkpoint control, response to DNA damage, as well as formation and export of mRNP-particles. We have identified the Num1 protein as the homologue of SPF27, one of NTC core components, in the basidiomycetous fungus Ustilago maydis. Num1 is required for polarized growth of the fungal hyphae, and, in line with the described NTC functions, the num1 mutation affects the cell cycle and cell division. The num1 deletion influences splicing in U. maydis on a global scale, as RNA-Seq analysis revealed increased intron retention rates. Surprisingly, we identified in a screen for Num1 interacting proteins not only NTC core components as Prp19 and Cef1, but several proteins with putative functions during vesicle-mediated transport processes. Among others, Num1 interacts with the motor protein Kin1 in the cytoplasm. Similar phenotypes with respect to filamentous and polar growth, vacuolar morphology, as well as the motility of early endosomes corroborate the genetic interaction between Num1 and Kin1. Our data implicate a previously unidentified connection between a component of the splicing machinery and cytoplasmic transport processes. As the num1 deletion also affects cytoplasmic mRNA transport, the protein may constitute a novel functional interconnection between the two disparate processes of splicing and trafficking.


Zdroje

1. BrefortT, DoehlemannG, Mendoza-MendozaA, ReissmannS, DjameiA, et al. (2009) Ustilago maydis as a Pathogen. Annu Rev Phytopathol 47: 423–445.

2. HeimelK, SchererM, VranesM, WahlR, PothiratanaC, et al. (2010) The transcription factor Rbf1 is the master regulator for b-mating type controlled pathogenic development in Ustilago maydis. PLoS Pathog 6: e1001035.

3. SteinbergG, Perez-MartinJ (2008) Ustilago maydis, a new fungal model system for cell biology. Trends Cell Biol 18: 61–67.

4. Wedlich-SöldnerR, BölkerM, KahmannR, SteinbergG (2000) A putative endosomal t-SNARE links exo- and endocytosis in the phytopathogenic fungus Ustilago maydis. EMBO J 19: 1974–1986.

5. StraubeA, EnardW, BernerA, Wedlich-SöldnerR, KahmannR, et al. (2001) A split motor domain in a cytoplasmic dynein. EMBO J 20: 5091–5100.

6. VollmeisterE, SchipperK, FeldbrüggeM (2012) Microtubule-dependent mRNA transport in the model microorganism Ustilago maydis. RNA Biol 9: 261–268.

7. BaumannS, PohlmannT, JungbluthM, BrachmannA, FeldbrüggeM (2012) Kinesin-3 and dynein mediate microtubule-dependent co-transport of mRNPs and endosomes. J Cell Sci 125(Pt 11): 2740–52.

8. Wedlich-SöldnerR, StraubeA, FriedrichMW, SteinbergG (2002) A balance of KIF1A-like kinesin and dynein organizes early endosomes in the fungus Ustilago maydis. EMBO J 21: 2946–2957.

9. LenzJH, SchuchardtI, StraubeA, SteinbergG (2006) A dynein loading zone for retrograde endosome motility at microtubule plus-ends. EMBO J 25: 2275–2286.

10. SchusterM, KilaruS, FinkG, CollemareJ, RogerY, et al. (2011) Kinesin-3 and dynein cooperate in long-range retrograde endosome motility along a nonuniform microtubule array. Mol Biol Cell 22: 3645–3657.

11. SchusterM, LipowskyR, AssmannMA, LenzP, SteinbergG (2011) Transient binding of dynein controls bidirectional long-range motility of early endosomes. Proc Natl Acad Sci U S A 108: 3618–3623.

12. SchusterM, KilaruS, AshwinP, LinC, SeversNJ, et al. (2011) Controlled and stochastic retention concentrates dynein at microtubule ends to keep endosomes on track. EMBO J 30: 652–664.

13. SteinbergG, SchliwaM, LehmlerC, BölkerM, KahmannR, et al. (1998) Kinesin from the plant pathogenic fungus Ustilago maydis is involved in vacuole formation and cytoplasmic migration. J Cell Sci 111(Pt 15): 2235–2246.

14. SchuchardtI, AssmannD, ThinesE, SchuberthC, SteinbergG (2005) Myosin-V, Kinesin-1, and Kinesin-3 cooperate in hyphal growth of the fungus Ustilago maydis. Mol Biol Cell 16: 5191–5201.

15. WeberI, AssmannD, ThinesE, SteinbergG (2006) Polar localizing class V myosin chitin synthases are essential during early plant infection in the plant pathogenic fungus Ustilago maydis. Plant Cell 18: 225–242.

16. TreitschkeS, DoehlemannG, SchusterM, SteinbergG (2010) The myosin motor domain of fungal chitin synthase V is dispensable for vesicle motility but required for virulence of the maize pathogen Ustilago maydis. Plant Cell 22: 2476–2494.

17. SchusterM, TreitschkeS, KilaruS, MolloyJ, HarmerNJ, et al. (2012) Myosin-5, kinesin-1 and myosin-17 cooperate in secretion of fungal chitin synthase. EMBO J 31: 214–227.

18. MakinoR, KamadaT (2004) Isolation and characterization of mutations that affect nuclear migration for dikaryosis in Coprinus cinereus. Curr Genet 45: 149–156.

19. NeubauerG, KingA, RappsilberJ, CalvioC, WatsonM, et al. (1998) Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex. Nat Genet 20: 46–50.

20. LehmlerC, SteinbergG, SnetselaarK, SchliwaM, KahmannR, et al. (1997) Identification of a motor protein required for filamentous growth in Ustilago maydis. EMBO J 16: 3464–3473.

21. GroteM, WolfE, WillCL, LemmI, AgafonovDE, et al. (2010) Molecular architecture of the human Prp19/CDC5L complex. Mol Cell Biol 30: 2105–2119.

22. ChelskyD, RalphR, JonakG (1989) Sequence requirements for synthetic peptide-mediated translocation to the nucleus. Mol Cell Biol 9: 2487–2492.

23. KämperJ, KahmannR, BölkerM, MaLJ, BrefortT, et al. (2006) Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis. Nature 444: 97–101.

24. BrachmannA, WeinzierlG, KämperJ, KahmannR (2001) Identification of genes in the bW/bE regulatory cascade in Ustilago maydis. Mol Microbiol 42: 1047–1063.

25. MitchisonJM, NurseP (1985) Growth in cell length in the fission yeast Schizosaccharomyces pombe. J Cell Sci 75: 357–376.

26. MatsuokaH, YangH-C, HommaT, NemotoY, YamadaS, et al. (1995) Use of Congo red as a microscopic fluorescence indicator of hyphal growth. Appl Microbiol Biotechnol 43: 102–108.

27. NagataY, BurgerMM (1974) Wheat germ agglutinin. Molecular characteristics and specificity for sugar binding. J Biol Chem 249: 3116–3122.

28. OhiMD, GouldKL (2002) Characterization of interactions among the Cef1p-Prp19p-associated splicing complex. Rna 8: 798–815.

29. NasmythK, NurseP (1981) Cell division cycle mutants altered in DNA replication and mitosis in the fission yeast Schizosaccharomyces pombe. Mol Gen Genetics 182: 119–124.

30. OhiR, McCollumD, HiraniB, Den HaeseGJ, ZhangX, et al. (1994) The Schizosaccharomyces pombe cdc5+ gene encodes an essential protein with homology to c-Myb. EMBO J 13: 471–483.

31. BernsteinHS, CoughlinSR (1998) A mammalian homolog of fission yeast Cdc5 regulates G2 progression and mitotic entry. J Biol Chem 273: 4666–4671.

32. HenriquesJA, MoustacchiE (1980) Isolation and characterization of pso mutants sensitive to photo-addition of psoralen derivatives in Saccharomyces cerevisiae. Genetics 95: 273–288.

33. GreyM, DüsterhöftA, HenriquesJA, BrendelM (1996) Allelism of PSO4 and PRP19 links pre-mRNA processing with recombination and error-prone DNA repair in Saccharomyces cerevisiae. Nucleic Acids Res 24: 4009–4014.

34. BrendelM, BonattoD, StraussM, ReversLF, PungartnikC, et al. (2003) Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae. Mutat Res 544: 179–193.

35. ZhangN, KaurR, LuX, ShenX, LiL, et al. (2005) The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links. J Biol Chem 280: 40559–40567.

36. BeckBD, ParkSJ, LeeYJ, RomanY, HromasRA, et al. (2008) Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair. J Biol Chem 283: 9023–9030.

37. LuX, LegerskiRJ (2007) The Prp19/Pso4 core complex undergoes ubiquitylation and structural alterations in response to DNA damage. Biochem Biophys Res Commun 354: 968–974.

38. LegerskiRJ (2009) The Pso4 complex splices into the DNA damage response. Cell Cycle 8: 3448–3449.

39. Garcia-MuseT, SteinbergG, Perez-MartinJ (2003) Pheromone-induced G2 arrest in the phytopathogenic fungus Ustilago maydis. Eukaryot Cell 2: 494–500.

40. MazzeiT (1984) Chemistry and mechanism of action of bleomycin. Chemioterapia : international journal of the Mediterranean Society of Chemotherapy 3: 316–319.

41. YarbroJW (1992) Mechanism of action of hydroxyurea. Semin Oncol 19: 1–10.

42. ReversLF, CardoneJM, BonattoD, SaffiJ, GreyM, et al. (2002) Thermoconditional modulation of the pleiotropic sensitivity phenotype by the Saccharomyces cerevisiae PRP19 mutant allele pso4-1. Nucleic Acids Res 30: 4993–5003.

43. Flor-ParraI, VranesM, KämperJ, Perez-MartinJ (2006) Biz1, a zinc finger protein required for plant invasion by Ustilago maydis, regulates the levels of a mitotic cyclin. Plant Cell 18: 2369–2387.

44. BanksGR, SheltonPA, KanugaN, HoldenDW, SpanosA (1993) The Ustilago maydis nar1 gene encoding nitrate reductase activity: sequence and transcriptional regulation. Gene 131: 69–78.

45. RiedlJ, CrevennaAH, KessenbrockK, YuJH, NeukirchenD, et al. (2008) Lifeact: a versatile marker to visualize F-actin. Nat Methods 5: 605–607.

46. StraubeA, BrillM, OakleyBR, HorioT, SteinbergG (2003) Microtubule organization requires cell cycle-dependent nucleation at dispersed cytoplasmic sites: polar and perinuclear microtubule organizing centers in the plant pathogen Ustilago maydis. Mol Biol Cell 14: 642–657.

47. BechtP, KönigJ, FeldbrüggeM (2006) The RNA-binding protein Rrm4 is essential for polarity in Ustilago maydis and shuttles along microtubules. J Cell Sci 119: 4964–4973.

48. RequenaN, Alberti-SeguiC, WinzenburgE, HornC, SchliwaM, et al. (2001) Genetic evidence for a microtubule-destabilizing effect of conventional kinesin and analysis of its consequences for the control of nuclear distribution in Aspergillus nidulans. Mol Microbiol 42: 121–132.

49. KonczC, DejongF, VillacortaN, SzakonyiD, KonczZ (2012) The spliceosome-activating complex: molecular mechanisms underlying the function of a pleiotropic regulator. Front Plant Sci 3: 9.

50. TarnWY, HsuCH, HuangKT, ChenHR, KaoHY, et al. (1994) Functional association of essential splicing factor(s) with PRP19 in a protein complex. EMBO J 13: 2421–2431.

51. HoggR, McGrailJC, O'KeefeRT (2010) The function of the NineTeen Complex (NTC) in regulating spliceosome conformations and fidelity during pre-mRNA splicing. Biochem Soc Trans 38: 1110–1115.

52. OhiMD, Vander KooiCW, RosenbergJA, ChazinWJ, GouldKL (2003) Structural insights into the U-box, a domain associated with multi-ubiquitination. Nat Struct Biol 10: 250–255.

53. OhiMD, Vander KooiCW, RosenbergJA, RenL, HirschJP, et al. (2005) Structural and functional analysis of essential pre-mRNA splicing factor Prp19p. Mol Cell Biol 25: 451–460.

54. ChengSC, TarnWY, TsaoTY, AbelsonJ (1993) PRP19: a novel spliceosomal component. Mol Cell Biol 13: 1876–1882.

55. TarnWY, LeeKR, ChengSC (1993) The yeast PRP19 protein is not tightly associated with small nuclear RNAs, but appears to associate with the spliceosome after binding of U2 to the pre-mRNA and prior to formation of the functional spliceosome. Mol Cell Biol 13: 1883–1891.

56. TarnWY, LeeKR, ChengSC (1993) Yeast precursor mRNA processing protein PRP19 associates with the spliceosome concomitant with or just after dissociation of U4 small nuclear RNA. Proc Natl Acad Sci U S A 90: 10821–10825.

57. TsaiWY, ChowYT, ChenHR, HuangKT, HongRI, et al. (1999) Cef1p is a component of the Prp19p-associated complex and essential for pre-mRNA splicing. J Biol Chem 274: 9455–9462.

58. McDonaldWH, OhiR, SmelkovaN, FrendeweyD, GouldKL (1999) Myb-related fission yeast cdc5p is a component of a 40S snRNP-containing complex and is essential for pre-mRNA splicing. Mol Cell Biol 19: 5352–5362.

59. QueryCC, KonarskaMM (2012) CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome. Rna 18: 1001–1013.

60. PleissJA, WhitworthGB, BergkesselM, GuthrieC (2007) Rapid, transcript-specific changes in splicing in response to environmental stress. Mol Cell 27: 928–937.

61. BöhmerC, BöhmerM, BölkerM, SandrockB (2008) Cdc42 and the Ste20-like kinase Don3 act independently in triggering cytokinesis in Ustilago maydis. J Cell Sci 121: 143–148.

62. BöhmerC, RippC, BölkerM (2009) The germinal centre kinase Don3 triggers the dynamic rearrangement of higher-order septin structures during cytokinesis in Ustilago maydis. Mol Microbiol 74: 1484–1496.

63. MahlertM, LevelekiL, HlubekA, SandrockB, BölkerM (2006) Rac1 and Cdc42 regulate hyphal growth and cytokinesis in the dimorphic fungus Ustilago maydis. Mol Microbiol 59: 567–578.

64. WeinzierlG, LevelekiL, HasselA, KostG, WannerG, et al. (2002) Regulation of cell separation in the dimorphic fungus Ustilago maydis. Mol Microbiol 45: 219–231.

65. FreitagJ, LanverD, BöhmerC, SchinkKO, BölkerM, et al. (2011) Septation of infectious hyphae is critical for appressoria formation and virulence in the smut fungus Ustilago maydis. PLoS Pathog 7: e1002044.

66. BankmannM, PrakashL, PrakashS (1992) Yeast RAD14 and human xeroderma pigmentosum group A DNA-repair genes encode homologous proteins. Nature 355: 555–558.

67. MahajanKN, MitchellBS (2003) Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase. Proc Natl Acad Sci U S A 100: 10746–10751.

68. AjuhP, KusterB, PanovK, ZomerdijkJC, MannM, et al. (2000) Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry. EMBO J 19: 6569–6581.

69. ZhangN, KaurR, AkhterS, LegerskiRJ (2009) Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. EMBO Rep 10: 1029–1035.

70. Perez-MartinJ (2009) DNA-damage response in the basidiomycete fungus Ustilago maydis relies in a sole Chk1-like kinase. DNA Repair 8: 720–731.

71. Perez-MartinJ, de Sena-TomasC (2011) Dikaryotic cell cycle in the phytopathogenic fungus Ustilago maydis is controlled by the DNA damage response cascade. Plant Signal Behav 6: 1574–1577.

72. ChorevM, CarmelL (2012) The function of introns. Frontiers in genetics 3: 55.

73. Le HirH, NottA, MooreMJ (2003) How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci 28: 215–220.

74. MuresanV, MuresanZ (2012) Unconventional functions of microtubule motors. Arch Biochem Biophys 520: 17–29.

75. SunF, ZhuC, DixitR, CavalliV (2011) Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO J 30: 3416–3429.

76. SteinbergG, SchusterM, TheisenU, KilaruS, ForgeA, et al. (2012) Motor-driven motility of fungal nuclear pores organizes chromosomes and fosters nucleocytoplasmic transport. J Cell Biol 198: 343–355.

77. KönigJ, BaumannS, KoepkeJ, PohlmannT, ZarnackK, et al. (2009) The fungal RNA-binding protein Rrm4 mediates long-distance transport of ubi1 and rho3 mRNAs. EMBO J 28: 1855–1866.

78. BechtP, VollmeisterE, FeldbrüggeM (2005) Role for RNA-binding proteins implicated in pathogenic development of Ustilago maydis. Eukaryot Cell 4: 121–133.

79. ZimyaninVL, BelayaK, PecreauxJ, GilchristMJ, ClarkA, et al. (2008) In vivo imaging of oskar mRNA transport reveals the mechanism of posterior localization. Cell 134: 843–853.

80. ChangYF, ImamJS, WilkinsonMF (2007) The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76: 51–74.

81. BrendzaRP, SerbusLR, SaxtonWM, DuffyJB (2002) Posterior localization of dynein and dorsal-ventral axis formation depend on kinesin in Drosophila oocytes. Curr Biol 12: 1541–1545.

82. ChanaratS, SeizlM, StrasserK (2011) The Prp19 complex is a novel transcription elongation factor required for TREX occupancy at transcribed genes. Genes Dev 25: 1147–1158.

83. KatahiraJ, YonedaY (2009) Roles of the TREX complex in nuclear export of mRNA. RNA Biol 6: 149–152.

84. KatahiraJ, StrasserK, PodtelejnikovA, MannM, JungJU, et al. (1999) The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J 18: 2593–2609.

85. Santos-RosaH, MorenoH, SimosG, SegrefA, FahrenkrogB, et al. (1998) Nuclear mRNA export requires complex formation between Mex67p and Mtr2p at the nuclear pores. Mol Cell Biol 18: 6826–6838.

86. SegrefA, SharmaK, DoyeV, HellwigA, HuberJ, et al. (1997) Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. EMBO J 16: 3256–3271.

87. Sambrook J, Frisch EF, Maniatis T (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbour, New York: Cold Spring Harbour Laboratory Press.

88. TsukudaT, CarletonS, FotheringhamS, HollomanWK (1988) Isolation and characterization of an autonomously replicating sequence from Ustilago maydis. Mol Cell Biol 8: 3703–3709.

89. Holliday R (1974) Ustilago maydis. In: King RC, editor. Handbook of Genetics. New York, USA: Plenum Press. pp. 575–595.

90. MahlertM, VoglerC, StelterK, HauseG, BasseCW (2009) The a2 mating-type-locus gene lga2 of Ustilago maydis interferes with mitochondrial dynamics and fusion, partially in dependence on a Dnm1-like fission component. J Cell Sci 122: 2402–2412.

91. MüllerP, WeinzierlG, BrachmannA, FeldbrüggeM, KahmannR (2003) Mating and pathogenic development of the Smut fungus Ustilago maydis are regulated by one mitogen-activated protein kinase cascade. Eukaryot Cell 2: 1187–1199.

92. PontecorvoG, RoperJA, HemmonsLM, MacdonaldKD, BuftonAW (1953) The genetics of Aspergillus nidulans. Adv Genet 5: 141–238.

93. Hill TWuK, E (2001) Improved protocols for Aspergillus minimal medium: trace element and minimal medium salt stock solutions. Fungal Genetics Newsletter 48: 20–21.

94. GillissenB, BergemannJ, SandmannC, SchröerB, BölkerM, et al. (1992) A two-component regulatory system for self/non-self recognition in Ustilago maydis. Cell 68: 647–657.

95. Mendoza-MendozaA, EskovaA, WeiseC, CzajkowskiR, KahmannR (2009) Hap2 regulates the pheromone response transcription factor prf1 in Ustilago maydis. Mol Microbiol 72: 683–698.

96. HoffmanCS, WinstonF (1987) A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of E. coli. Gene 57: 267–272.

97. SchulzB, BanuettF, DahlM, SchlesingerR, SchäferW, et al. (1990) The b alleles of U. maydis, whose combinations program pathogenic development, code for polypeptides containing a homeodomain-related motif. Cell 60: 295–306.

98. TimberlakeWE, MarshallMA (1989) Genetic engineering of filamentous fungi. Science 244: 1313–1317.

99. YeltonMM, HamerJE, TimberlakeWE (1984) Transformation of Aspergillus nidulans by using a trpC plasmid. Proc Natl Acad Sci U S A 81: 1470–1474.

100. KämperJ (2004) A PCR-based system for highly efficient generation of gene replacement mutants in Ustilago maydis. Mol Genet Genomics 271: 103–110.

101. BrachmannA, KönigJ, JuliusC, FeldbrüggeM (2004) A reverse genetic approach for generating gene replacement mutants in Ustilago maydis. Mol Genet Genomics 272: 216–226.

102. SchererM, HeimelK, StarkeV, KämperJ (2006) The Clp1 protein is required for clamp formation and pathogenic development of Ustilago maydis. Plant Cell 18: 2388–2401.

103. HeimelK, SchererM, SchulerD, KämperJ (2010) The Ustilago maydis Clp1 protein orchestrates pheromone and b-dependent signaling pathways to coordinate the cell cycle and pathogenic development. Plant Cell 22: 2908–2922.

104. GarridoE, Perez-MartinJ (2003) The crk1 gene encodes an Ime2-related protein that is required for morphogenesis in the plant pathogen Ustilago maydis. Mol Microbiol 47: 729–743.

105. TrapnellC, PachterL, SalzbergSL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105–1111.

106. AndersS, HuberW (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106.

107. HardcastleTJ, KellyKA (2010) baySeq: empirical Bayesian methods for identifying differential expression in sequence count data. BMC Bioinformatics 11: 422.

108. LanverD, Mendoza-MendozaA, BrachmannA, KahmannR (2010) Sho1 and Msb2-related proteins regulate appressorium development in the smut fungus Ustilago maydis. Plant Cell 22: 2085–2101.

109. AbramoffMD, MagalhaesPJ, RamSJ (2004) Image Processing with Image J. Biophotonics International 11: 36–42.

110. KatohK, TohH (2008) Recent developments in the MAFFT multiple sequence alignment program. Brief Bioinform 9: 286–298.

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