The RNA-binding Proteins FMR1, Rasputin and Caprin Act Together with the UBA Protein Lingerer to Restrict Tissue Growth in

English version České info

Appropriate expression of growth-regulatory genes is essential to ensure normal animal development and to prevent diseases like cancer. Gene regulation at the levels of transcription and translational initiation mediated by the Hippo and Insulin signaling pathways and by the TORC1 complex, respectively, has been well documented. Whether translational control mediated by RNA-binding proteins contributes to the regulation of cellular growth is less clear. Here, we identify Lingerer (Lig), an UBA domain-containing protein, as growth suppressor that associates with the RNA-binding proteins Fragile X mental retardation protein 1 (FMR1) and Caprin (Capr) and directly interacts with and regulates the RNA-binding protein Rasputin (Rin) in Drosophila melanogaster. lig mutant organs overgrow due to increased proliferation, and a reporter for the JAK/STAT signaling pathway is upregulated in a lig mutant situation. rin, Capr or FMR1 in combination as double mutants, but not the respective single mutants, display lig like phenotypes, implicating a redundant function of Rin, Capr and FMR1 in growth control in epithelial tissues. Thus, Lig regulates cell proliferation during development in concert with Rin, Capr and FMR1.

Vyšlo v časopise: The RNA-binding Proteins FMR1, Rasputin and Caprin Act Together with the UBA Protein Lingerer to Restrict Tissue Growth in. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003598
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003598

Souhrn

Zdroje

1. TumanengK, RussellRC, GuanK-L (2012) Organ size control by Hippo and TOR pathways. Curr Biol 22: R368–R379.

2. LuoY, ShanG, GuoW, SmrtRD, JohnsonEB, et al. (2010) Fragile X mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells. PLoS Genet 6: e1000898.

3. LypowyJ, ChenI-Y, AbdellatifM (2005) An alliance between Ras GTPase-activating protein, filamin C, and Ras GTPase-activating protein SH3 domain-binding protein regulates myocyte growth. J Biol Chem 280: 25717–25728.

4. SolomonS, XuY, WangB, DavidMD, SchubertP, et al. (2007) Distinct structural features of caprin-1 mediate its interaction with G3BP-1 and its induction of phosphorylation of eukaryotic translation initiation factor 2alpha, entry to cytoplasmic stress granules, and selective interaction with a subset of mRNAs. Mol Cell Biol 27: 2324–2342.

5. BikkavilliRK, MalbonCC (2011) Arginine methylation of G3BP1 in response to Wnt3a regulates β-catenin mRNA. J Cell Sci 124: 2310–2320.

6. YangY, XuS, XiaL, WangJ, WenS, et al. (2009) The bantam microRNA is associated with Drosophila fragile X mental retardation protein and regulates the fate of germline stem cells. PLoS Genet 5: e1000444.

7. CallanMA, CabernardC, HeckJ, LuoisS, DoeCQ, et al. (2010) Fragile X protein controls neural stem cell proliferation in the Drosophila brain. Hum Mol Genet 19: 3068–3079.

8. Fatimy ElR, TremblayS, DuryAY, SolomonS, De KoninckP, et al. (2012) Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes. PLoS ONE 7: e39338.

9. PapoulasO, MonzoKF, CantinGT, RuseC, YatesJR, et al. (2010) dFMRP and Caprin, translational regulators of synaptic plasticity, control the cell cycle at the Drosophila mid-blastula transition. Development 137: 4201–4209.

10. GrillB, WilsonGM, ZhangK-X, WangB, DoyonnasR, et al. (2004) Activation/division of lymphocytes results in increased levels of cytoplasmic activation/proliferation-associated protein-1: prototype of a new family of proteins. J Immunol 172: 2389–2400.

11. WangB, DavidMD, SchraderJW (2005) Absence of caprin-1 results in defects in cellular proliferation. J Immunol 175: 4274–4282.

12. GallouziIE, ParkerF, ChebliK, MaurierF, LabourierE, et al. (1998) A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability. Mol Cell Biol 18: 3956–3965.

13. TourrièreH, GallouziIE, ChebliK, CaponyJP, MouaikelJ, et al. (2001) RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization. Mol Cell Biol 21: 7747–7760.

14. HafenE (2004) Cancer, type 2 diabetes, and ageing: news from flies and worms. Swiss Med Wkly 134: 711–719.

15. KuniyoshiH, BabaK, UedaR, KondoS, AwanoW, et al. (2002) lingerer, a Drosophila gene involved in initiation and termination of copulation, encodes a set of novel cytoplasmic proteins. Genetics 162: 1775–1789.

16. RyooHD, BergmannA, GonenH, CiechanoverA, StellerH (2002) Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1. Nat Cell Biol 4: 432–438.

17. MartinFA, Pérez-GarijoA, MorataG (2009) Apoptosis in Drosophila: compensatory proliferation and undead cells. Int J Dev Biol 53: 1341–1347.

18. CostaA, WangY, DockendorffTC, Erdjument-BromageH, TempstP, et al. (2005) The Drosophila fragile X protein functions as a negative regulator in the orb autoregulatory pathway. Dev Cell 8: 331–342.

19. BarbeeSA, EstesPS, CzikoA-M, HillebrandJ, LuedemanRA, et al. (2006) Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P bodies. Neuron 52: 997–1009.

20. BeermanRW, JongensTA (2011) A non-canonical start codon in the Drosophila fragile X gene yields two functional isoforms. Neuroscience 181: 48–66.

21. Behm-AnsmantI, RehwinkelJ, DoerksT, StarkA, BorkP, et al. (2006) mRNA degradation by miRNAs and GW182 requires both CCR4∶NOT deadenylase and DCP1∶DCP2 decapping complexes. Genes Dev 20: 1885–1898.

22. StewartM, BakerRP, BaylissR, ClaytonL, GrantRP, et al. (2001) Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import. FEBS Lett 498: 145–149.

23. FribourgS, BraunIC, IzaurraldeE, ContiE (2001) Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. Mol Cell 8: 645–656.

24. BaylissR, LittlewoodT, StrawnLA, WenteSR, StewartM (2002) GLFG and FxFG nucleoporins bind to overlapping sites on importin-beta. J Biol Chem 277: 50597–50606.

25. VognsenT, KristensenO (2012) Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster. Biochem Biophys Res Commun 420: 188–192.

26. FrancoM, SeyfriedNT, BrandAH, PengJ, MayorU (2011) A novel strategy to isolate ubiquitin conjugates reveals wide role for ubiquitination during neural development. Mol Cell Proteomics 10: M110.002188.

27. NoloR, MorrisonCM, TaoC, ZhangX, HalderG (2006) The bantam microRNA is a target of the Hippo tumor-suppressor pathway. Curr Biol 16: 1895–1904.

28. ThompsonBJ, CohenSM (2006) The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell 126: 767–774.

29. BrenneckeJ, HipfnerDR, StarkA, RussellRB, CohenSM (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113: 25–36.

30. EpsteinAM, BauerCR, HoA, BoscoG, ZarnescuDC (2009) Drosophila Fragile X protein controls cellular proliferation by regulating cbl levels in the ovary. Dev Biol 330: 83–92.

31. CallanMA, ClementsN, AhrendtN, ZarnescuDC (2012) Fragile X protein is required for inhibition of insulin signaling and regulates glial-dependent neuroblast reactivation in the developing brain. Brain Res 1462: 151–161.

32. MüllerP, KuttenkeulerD, GesellchenV, ZeidlerMP, BoutrosM (2005) Identification of JAK/STAT signalling components by genome-wide RNA interference. Nature 436: 871–875.

33. KuniyoshiH, Usui-AokiK, JuniN, YamamotoD (2003) Expression analysis of the lingerer gene in the larval central nervous system of Drosophila melanogaster. J Neurogenet 17: 117–137.

34. NazRK, DhandapaniL (2010) Identification of human sperm proteins that interact with human zona pellucida 3 (ZP3) using yeast two-hybrid system. J Reprod Immunol 84: 24–31.

35. WildeIB, BrackM, WingetJM, MayorT (2011) Proteomic characterization of aggregating proteins after the inhibition of the ubiquitin proteasome system. J Proteome Res 10: 1062–1072.

36. CzikoA-MJ, McCannCT, HowlettIC, BarbeeSA, DuncanRP, et al. (2009) Genetic modifiers of dFMR1 encode RNA granule components in Drosophila. Genetics 182: 1051–1060.

37. ArbouzovaNI, ZeidlerMP (2006) JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development 133: 2605–2616.

38. YoonWH, MeinhardtH, MontellDJ (2011) miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold. Nat Cell Biol 13: 1062–1069.

39. LuoW, SehgalA (2012) Regulation of circadian behavioral output via a microRNA-JAK/STAT circuit. Cell 148: 765–779.

40. AtlasR, BeharL, ElliottE, GinzburgI (2004) The insulin-like growth factor mRNA binding-protein IMP-1 and the Ras-regulatory protein G3BP associate with tau mRNA and HuD protein in differentiated P19 neuronal cells. J Neurochem 89: 613–626.

41. AtlasR, BeharL, SapoznikS, GinzburgI (2007) Dynamic association with polysomes during P19 neuronal differentiation and an untranslated-region-dependent translation regulation of the tau mRNA by the tau mRNA-associated proteins IMP1, HuD, and G3BP1. J Neurosci Res 85: 173–183.

42. ZhangYQ, BaileyAM, MatthiesHJ, RendenRB, SmithMA, et al. (2001) Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107: 591–603.

43. Bettencourt da CruzA, SchwärzelM, SchulzeS, NiyyatiM, HeisenbergM, et al. (2005) Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila. Mol Biol Cell 16: 2433–2442.

44. GaryJD, ClarkeS (1998) RNA and protein interactions modulated by protein arginine methylation. Prog Nucleic Acid Res Mol Biol 61: 65–131.

45. BedfordMT, ClarkeSG (2009) Protein arginine methylation in mammals: who, what, and why. Mol Cell 33: 1–13.

46. StetlerA, WinogradC, SayeghJ, CheeverA, PattonE, et al. (2006) Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp. Hum Mol Genet 15: 87–96.

47. PahlichS, ZakaryanRP, GehringH (2008) Identification of proteins interacting with Protein arginine methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent of its methylation state. Proteins 72: 1125–1137.

48. PazmanC, MayesCA, FantoM, HaynesSR, MlodzikM (2000) Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling. Development 127: 1715–1725.

49. NewsomeTP, AslingB, DicksonBJ (2000) Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development 127: 851–860.

50. NeufeldTP, la Cruz deAF, JohnstonLA, EdgarBA (1998) Coordination of growth and cell division in the Drosophila wing. Cell 93: 1183–1193.

51. CallejaM, MorenoE, PelazS, MorataG (1996) Visualization of gene expression in living adult Drosophila. Science 274: 252–255.

52. MorrisonCM, HalderG (2009) Characterization of a dorsal-eye Gal4 Line in Drosophila. Genesis 48: 3–7.

53. HazelettDJ, BourouisM, WalldorfU, TreismanJE (1998) decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc. Development 125: 3741–3751.

54. KnoblichJA, SauerK, JonesL, RichardsonH, SaintR, et al. (1994) Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. Cell 77: 107–120.

55. DockendorffTC, SuHS, McBrideSMJ, YangZ, ChoiCH, et al. (2002) Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 34: 973–984.

56. ZhangL, RenF, ZhangQ, ChenY, WangB, et al. (2008) The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. Dev Cell 14: 377–387.

57. BachEA, EkasLA, Ayala-CamargoA, FlahertyMS, LeeH, et al. (2007) GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns 7: 323–331.

58. GludererS, OldhamS, RintelenF, SulzerA, SchüttC, et al. (2008) Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth. BMC Dev Biol 8: 10.

59. VenkenK, CarlsonJ, SchulzeK, PanH, HeY, et al. (2009) Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster. Nat Methods 6: 431–434.

60. BischofJ, MaedaRK, HedigerM, KarchF, BaslerK (2007) An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases. Proc Natl Acad Sci USA 104: 3312–3317.

61. EulalioA, Behm-AnsmantI, SchweizerD, IzaurraldeE (2007) P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol Cell Biol 27: 3970–3981.

62. GludererS, BrunnerE, GermannM, JovaisaiteV, LiC, et al. (2010) Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila. J Biol 9: 9.

63. MiyoshiK, TsukumoH, NagamiT, SiomiH, SiomiMC (2005) Slicer function of Drosophila Argonautes and its involvement in RISC formation. Genes Dev 19: 2837–2848.

64. WanL, DockendorffTC, JongensTA, DreyfussG (2000) Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. Mol Cell Biol 20: 8536–8547.

65. MainesJZ, StevensLM, TongX, SteinD (2004) Drosophila dMyc is required for ovary cell growth and endoreplication. Development 131: 775–786.

66. ChenH-W, ChenX, OhS-W, MarinissenMJ, GutkindJS, et al. (2002) mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family. Genes Dev 16: 388–398.