Stress Granule-Defective Mutants Deregulate Stress Responsive Transcripts

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When cells encounter harsh conditions, they face an energy crisis since the stress will reduce their energy production, and at the same time cause extra demands on energy expenditure. To tackle this dilemma, cells under stress form giant agglomerates of RNA and protein, called stress granules. In these, mRNA molecules are kept silent, preventing waste of energy on producing proteins not needed under these conditions. A few mRNAs, encoding proteins required for the cell to survive, stay outside of stress granules and escape this silencing. This mechanism can protect plants and microbes against cold spells or heat shocks, and human cells exposed to oxidative damage or toxic drugs. We have investigated which genes are necessary to form stress granules, and their impact on the stress response. We discovered that mutant cells unable to form stress granules overreacted to stress, in that they produced much higher levels of the induced mRNAs. We think this means that gene regulatory proteins are sequestered inside stress granules, inhibiting their action. Stress granules may thus function as moderators that dampen the stress response, safeguarding the cell against excessive reactions.

Vyšlo v časopise: Stress Granule-Defective Mutants Deregulate Stress Responsive Transcripts. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004763
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004763

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Zdroje

1. GrigullJ, MnaimnehS, PootoolalJ, RobinsonMD, HughesTR (2004) Genome-wide analysis of mRNA stability using transcription inhibitors and microarrays reveals posttranscriptional control of ribosome biogenesis factors. Mol Cell Biol 24: 5534–5547.

2. MolinC, JauhiainenA, WarringerJ, NermanO, SunnerhagenP (2009) mRNA stability changes precede changes in steady-state mRNA amounts during hyperosmotic stress. RNA 15: 600–614.

3. Romero-SantacreuL, MorenoJ, Pérez-OrtínJE, AlepuzP (2009) Specific and global regulation of mRNA stability during osmotic stress in Saccharomyces cerevisiae. RNA 15: 1110–1120.

4. WarringerJ, HultM, RegotS, PosasF, SunnerhagenP (2010) The HOG pathway dictates the short-term translational response after hyperosmotic shock. Mol Biol Cell 21: 3080–3092.

5. MelamedD, PnueliL, AravaY (2008) Yeast translational response to high salinity: Global analysis reveals regulation at multiple levels. RNA 14: 1337–1351.

6. ShentonD, SmirnovaJB, SelleyJN, CarrollK, HubbardSJ, et al. (2006) Global translational responses to oxidative stress impact upon multiple levels of protein synthesis. J Biol Chem 281: 29011–29021.

7. GarreE, Romero-SantacreuL, De ClercqN, BlascoN, SunnerhagenP, et al. (2012) The yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for rapid reprogramming of translation after hyperosmotic shock. Mol Biol Cell 23: 137–150.

8. KedershaN, IvanovP, AndersonP (2013) Stress granules and cell signaling: more than just a passing phase? Trends Biochem Sci 38: 494–506.

9. BuchanJR, ParkerR (2009) Eukaryotic stress granules: the ins and outs of translation. Mol Cell 36: 932–941.

10. AndersonP, KedershaN (2008) Stress granules: the Tao of RNA triage. Trends Biochem Sci 33: 141–150.

11. BuchanJR, MuhlradD, ParkerR (2008) P bodies promote stress granule assembly in Saccharomyces cerevisiae. J Cell Biol 183: 441–455.

12. ShahKH, ZhangB, RamachandranV, HermanPK (2013) Processing body and stress granule assembly occur by independent and differentially regulated pathways in Saccharomyces cerevisiae. Genetics 193: 109–123.

13. HoyleNP, CastelliLM, CampbellSG, HolmesLE, AsheMP (2007) Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies. J Cell Biol 179: 65–74.

14. OhnT, KedershaN, HickmanT, TisdaleS, AndersonP (2008) A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly. Nat Cell Biol 10: 1224–1231.

15. TakaharaT, MaedaT (2012) Transient sequestration of TORC1 into stress granules during heat stress. Mol Cell 47: 242–252.

16. ArimotoK, FukudaH, Imajoh-OhmiS, SaitoH, TakekawaM (2008) Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways. Nat Cell Biol 10: 1324–1332.

17. TakahashiM, HiguchiM, MatsukiH, YoshitaM, OhsawaT, et al. (2012) Stress granules inhibit apoptosis by reducing reactive oxygen species production. Mol Cell Biol 33: 815–829.

18. WangC-Y, WenW-L, NilssonD, SunnerhagenP, ChangT-H, et al. (2012) Analysis of stress granule assembly in Schizosaccharomyces pombe. RNA 18: 694–703.

19. RamaswamiM, TaylorJP, ParkerR (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154: 727–736.

20. DidiotMC, SubramanianM, FlatterE, MandelJL, MoineH (2009) Cells lacking the fragile X mental retardation protein (FMRP) have normal RISC activity but exhibit altered stress granule assembly. Mol Biol Cell 20: 428–437.

21. KedershaNL, GuptaM, LiW, MillerI, AndersonP (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol 147: 1431–1442.

22. GrouslT, IvanovP, FrydlovaI, VasicovaP, JandaF, et al. (2009) Robust heat shock induces eIF2alpha-phosphorylation-independent assembly of stress granules containing eIF3 and 40S ribosomal subunits in budding yeast, Saccharomyces cerevisiae. J Cell Sci 122: 2078–2088.

23. WenWL, StevensonAL, WangCY, ChenHJ, KearseySE, et al. (2010) Vgl1, a multi-KH domain protein, is a novel component of the fission yeast stress granules required for cell survival under thermal stress. Nucleic Acids Res 38: 6555–6566.

24. NilssonD, SunnerhagenP (2011) Cellular stress induces cytoplasmic RNA granules in fission yeast. RNA 17: 120–133.

25. BuchanJR, YoonJH, ParkerR (2011) Stress-specific composition, assembly and kinetics of stress granules in Saccharomyces cerevisiae. J Cell Sci 124: 228–239.

26. GrouslT, IvanovP, MalcovaI, PompachP, FrydlovaI, et al. (2013) Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae. PLoS One 8: e57083.

27. BuchanJR, KolaitisRM, TaylorJP, ParkerR (2013) Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153: 1461–1474.

28. DuboulozF, DelocheO, WankeV, CameroniE, De VirgilioC (2005) The TOR and EGO protein complexes orchestrate microautophagy in yeast. Mol Cell 19: 15–26.

29. KedershaN, ChoMR, LiW, YaconoPW, ChenS, et al. (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol 151: 1257–1268.

30. ShethU, ParkerR (2003) Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300: 805–808.

31. KatoM, HanTW, XieS, ShiK, DuX, et al. (2012) Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149: 753–767.

32. LiX, KahveciT (2006) A novel algorithm for identifying low-complexity regions in a protein sequence. Bioinformatics 22: 2980–2987.

33. MalinovskaL, KroschwaldS, AlbertiS (2013) Protein disorder, prion propensities, and self-organizing macromolecular collectives. Biochim Biophys Acta 1834: 918–31.

34. MeszarosB, SimonI, DosztanyiZ (2009) Prediction of protein binding regions in disordered proteins. PLoS Comput Biol 5: e1000376.

35. ToombsJA, PetriM, PaulKR, KanGY, Ben-HurA, et al. (2012) De novo design of synthetic prion domains. Proc Natl Acad Sci U S A 109: 6519–6524.

36. DavidsonJF, SchiestlRH (2001) Cytotoxic and genotoxic consequences of heat stress are dependent on the presence of oxygen in Saccharomyces cerevisiae. J Bacteriol 183: 4580–4587.

37. BindaM, Peli-GulliMP, BonfilsG, PanchaudN, UrbanJ, et al. (2009) The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell 35: 563–573.

38. LiZ, VizeacoumarFJ, BahrS, LiJ, WarringerJ, et al. (2011) Systematic exploration of essential yeast gene function with temperature-sensitive mutants. Nat Biotechnol 29: 361–367.

39. EfeyanA, ZoncuR, ChangS, GumperI, SnitkinH, et al. (2013) Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature 493: 679–683.

40. TudiscaV, RecouvreuxV, MorenoS, Boy-MarcotteE, JacquetM, et al. (2010) Differential localization to cytoplasm, nucleus or P-bodies of yeast PKA subunits under different growth conditions. Eur J Cell Biol 89: 339–348.

41. WelkerS, RudolphB, FrenzelE, HagnF, LiebischG, et al. (2010) Hsp12 is an intrinsically unstructured stress protein that folds upon membrane association and modulates membrane function. Mol Cell 39: 507–520.

42. JorgensenP, RupesI, SharomJR, SchneperL, BroachJR, et al. (2004) A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. Genes Dev 18: 2491–2505.

43. UrbanJ, SoulardA, HuberA, LippmanS, MukhopadhyayD, et al. (2007) Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol Cell 26: 663–674.

44. HohmannS (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66: 300–372.

45. CherkasovaVA, HinnebuschAG (2003) Translational control by TOR and TAP42 through dephosphorylation of eIF2alpha kinase GCN2. Genes Dev 17: 859–872.

46. MitchellSF, JainS, SheM, ParkerR (2013) Global analysis of yeast mRNPs. Nat Struct Mol Biol 20: 127–133.

47. BoscoDA, LemayN, KoHK, ZhouH, BurkeC, et al. (2010) Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum Mol Genet 19: 4160–4175.

48. CastellaniRJ, GuptaY, ShengB, SiedlakSL, HarrisPL, et al. (2011) A novel origin for granulovacuolar degeneration in aging and Alzheimer's disease: parallels to stress granules. Lab Invest 91: 1777–1786.

49. HanTW, KatoM, XieS, WuLC, MirzaeiH, et al. (2012) Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell 149: 768–779.

50. SchürmannA, BrauersA, MassmannS, BeckerW, JoostHG (1995) Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. J Biol Chem 270: 28982–28988.

51. NakashimaN, HayashiN, NoguchiE, NishimotoT (1996) Putative GTPase Gtr1p genetically interacts with the RanGTPase cycle in Saccharomyces cerevisiae. J Cell Sci 109: 2311–2318.

52. GaoM, KaiserCA (2006) A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast. Nat Cell Biol 8: 657–667.

53. SancakY, PetersonTR, ShaulYD, LindquistRA, ThoreenCC, et al. (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320: 1496–1501.

54. SekiguchiT, HayashiN, WangY, KobayashiH (2008) Genetic evidence that Ras-like GTPases, Gtr1p, and Gtr2p, are involved in epigenetic control of gene expression in Saccharomyces cerevisiae. Biochem Biophys Res Commun 368: 748–754.

55. SeiserRM, SundbergAE, WollamBJ, Zobel-ThroppP, BaldwinK, et al. (2006) Ltv1 is required for efficient nuclear export of the ribosomal small subunit in Saccharomyces cerevisiae. Genetics 174: 679–691.

56. TodakaY, WangY, TashiroK, NakashimaN, NishimotoT, et al. (2005) Association of the GTP-binding protein Gtr1p with Rpc19p, a shared subunit of RNA polymerase I and III in yeast Saccharomyces cerevisiae. Genetics 170: 1515–1524.

57. MahboubiH, SeganathyE, KongD, StochajU (2013) Identification of novel stress granule components that are involved in nuclear transport. PLoS One 8: e68356.

58. ArhzaouyK, Ramezani-RadM (2012) Nuclear import of UBL-domain protein Mdy2 is required for heat-induced stress response in Saccharomyces cerevisiae. PLoS One 7: e52956.

59. HaimovichG, MedinaDA, CausseSZ, GarberM, Millan-ZambranoG, et al. (2013) Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis. Cell 153: 1000–1011.

60. ReinekeLC, DoughertyJD, PierreP, LloydRE (2012) Large G3BP-induced granules trigger eIF2alpha phosphorylation. Mol Biol Cell 23: 3499–3510.

61. DeinertK, FasioloF, HurtEC, SimosG (2001) Arc1p organizes the yeast aminoacyl-tRNA synthetase complex and stabilizes its interaction with the cognate tRNAs. J Biol Chem 276: 6000–6008.

62. YamasakiS, IvanovP, HuGF, AndersonP (2009) Angiogenin cleaves tRNA and promotes stress-induced translational repression. J Cell Biol 185: 35–42.

63. TongAH, EvangelistaM, ParsonsAB, XuH, BaderGD, et al. (2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294: 2364–2368.

64. TongAH, LesageG, BaderGD, DingH, XuH, et al. (2004) Global mapping of the yeast genetic interaction network. Science 303: 808–813.

65. HoCH, MagtanongL, BarkerSL, GreshamD, NishimuraS, et al. (2009) A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds. Nat Biotechnol 27: 369–377.

66. BoyleEI, WengS, GollubJ, JinH, BotsteinD, et al. (2004) GO Term Finder - open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics 20: 3710–3715.

67. BreitkreutzBJ, StarkC, TyersM (2003) Osprey: a network visualization system. Genome Biol 4: R22.

68. BreitkreutzBJ, StarkC, RegulyT, BoucherL, BreitkreutzA, et al. (2008) The BioGRID Interaction Database: 2008 update. Nucleic Acids Res 36: D637–640.

69. PettersenEF, GoddardTD, HuangCC, CouchGS, GreenblattDM, et al. (2004) UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem 25: 1605–1612.

70. Ben-ShemA, Garreau de LoubresseN, MelnikovS, JennerL, YusupovaG, et al. (2011) The structure of the eukaryotic ribosome at 3.0 Å resolution. Science 334: 1524–1529.

71. WarringerJ, BlombergA (2003) Automated screening in environmental arrays allows analysis of quantitative phenotypic profiles in Saccharomyces cerevisiae. Yeast 20: 53–67.

72. GockeE, ManneyTR (1979) Expression of radiation-induced mutations at the arginine permease (CAN1) locus in Saccharomyces cerevisiae. Genetics 91: 53–66.

73. Miller JH (1972) Experiments in molecular genetics. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press. pp. 352–355.

74. TompaP, DosztanyiZ, SimonI (2006) Prevalent structural disorder in E. coli and S. cerevisiae proteomes. J Proteome Res 5: 1996–2000.