Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae

English version

Autoři: Koji Kasahara ^aff001; Risa Nakayama ^aff002; Yuh Shiwa ^aff001; Yu Kanesaki ^aff003; Taichiro Ishige ^aff004; Hirofumi Yoshikawa ^aff002; Tetsuro Kokubo ^aff005
Působiště autorů: Department of Molecular Microbiology, Tokyo University of Agriculture, Tokyo, Japan ^aff001; Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan ^aff002; Research Institute of Green Science and Technology, Shizuoka University, Shizuoka, Japan ^aff003; NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo, Japan ^aff004; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan ^aff005
Vyšlo v časopise: Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008865
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008865

Souhrn

Fpr1 (FK506-sensitive proline rotamase 1), a protein of the FKBP12 (FK506-binding protein 12 kDa) family in Saccharomyces cerevisiae, is a primary target for the immunosuppressive agents FK506 and rapamycin. Fpr1 inhibits calcineurin and TORC1 (target of rapamycin complex 1) when bound to FK506 and rapamycin, respectively. Although Fpr1 is recognised to play a crucial role in the efficacy of these drugs, its physiological functions remain unclear. In a hmo1Δ (high mobility group family 1-deleted) yeast strain, deletion of FPR1 induced severe growth defects, which could be alleviated by increasing the copy number of RPL25 (ribosome protein of the large subunit 25), suggesting that RPL25 expression was affected in hmo1Δfpr1Δ cells. In the current study, extensive chromatin immunoprecipitation (ChIP) and ChIP-sequencing analyses revealed that Fpr1 associates specifically with the upstream activating sequences of nearly all RPG (ribosomal protein gene) promoters, presumably in a manner dependent on Rap1 (repressor/activator site binding protein 1). Intriguingly, Fpr1 promotes the binding of Fhl1/Ifh1 (forkhead-like 1/interacts with forkhead 1), two key regulators of RPG transcription, to certain RPG promoters independently of and/or cooperatively with Hmo1. Furthermore, mutation analyses of Fpr1 indicated that for transcriptional function on RPG promoters, Fpr1 requires its N-terminal domain and the binding surface for rapamycin, but not peptidyl-prolyl isomerase activity. Notably, Fpr1 orthologues from other species also inhibit TORC1 when bound to rapamycin, but do not regulate transcription in yeast, which suggests that these two functions of Fpr1 are independent of each other.

Klíčová slova:

Cell binding – Cell binding assay – DNA transcription – DNA-binding proteins – Saccharomyces cerevisiae – Transcriptional control – Yeast – Chromatin immunoprecipitation

Zdroje

1. Warner JR. The economics of ribosome biosynthesis in yeast. Trends Biochem Sci. 1999; 24(11):437–440. doi: 10.1016/s0968-0004(99)01460-7 10542411.

2. Ban N, Beckmann R, Cate JH, Dinman JD, Dragon F, Ellis SR, et al. A new system for naming ribosomal proteins. Curr Opin Struct Biol. 2014; 24 : 165–169. [pii] doi: 10.1016/j.sbi.2014.01.002 24524803.

3. Lempiainen H, Shore D. Growth control and ribosome biogenesis. Curr Opin Cell Biol. 2009; 21(6):855–863. [pii] doi: 10.1016/j.ceb.2009.09.002 19796927.

4. Albert B, Colleran C, Leger-Silvestre I, Berger AB, Dez C, Normand C, et al. Structure-function analysis of Hmo1 unveils an ancestral organization of HMG-Box factors involved in ribosomal DNA transcription from yeast to human. Nucleic Acids Res. 2013; 41(22):10135–10149. doi: 10.1093/nar/gkt770 24021628.

5. Heitman J, Movva NR, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science. 1991; 253(5022):905–909. doi: 10.1126/science.1715094 1715094.

6. Zaragoza D, Ghavidel A, Heitman J, Schultz MC. Rapamycin induces the G0 program of transcriptional repression in yeast by interfering with the TOR signaling pathway. Mol Cell Biol. 1998; 18(8):4463–4470. doi: 10.1128/mcb.18.8.4463 9671456.

7. Chiu MI, Katz H, Berlin V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci U S A. 1994; 91(26):12574–12578. doi: 10.1073/pnas.91.26.12574 7809080.

8. Sabers CJ, Martin MM, Brunn GJ, Williams JM, Dumont FJ, Wiederrecht G, et al. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem. 1995; 270(2):815–822. doi: 10.1074/jbc.270.2.815 7822316.

9. Harding MW, Galat A, Uehling DE, Schreiber SL. A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature. 1989; 341(6244):758–760. doi: 10.1038/341758a0 2477715.

10. Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today. 1992; 13(4):136–142. doi: 10.1016/0167-5699(92)90111-J 1374612.

11. Breuder T, Hemenway CS, Movva NR, Cardenas ME, Heitman J. Calcineurin is essential in cyclosporin A -⁠ and FK506-sensitive yeast strains. Proc Natl Acad Sci U S A. 1994; 91(12):5372–5376. doi: 10.1073/pnas.91.12.5372 7515500.

12. Cardenas ME, Zhu D, Heitman J. Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin. Curr Opin Nephrol Hypertens. 1995; 4(6):472–477. doi: 10.1097/00041552-199511000-00002 8591053.

13. Galat. Peptidyl-prolyl cis/trans isomerase. Oxford Univ Press. 1998. doi: 10.1016/s0140-6736(89)90417-0 PMID: 2568561.

14. Bonner JM, Boulianne GL. Diverse structures, functions and uses of FK506 binding proteins. Cell Signal. 2017; 38 : 97–105. doi: 10.1016/j.cellsig.2017.06.013 28652145.

15. Tong M, Jiang Y. FK506-Binding Proteins and Their Diverse Functions. Curr Mol Pharmacol. 2015; 9(1):48–65. doi: 10.2174/1874467208666150519113541 25986568.

16. Arevalo-Rodriguez M, Wu X, Hanes SD, Heitman J. Prolyl isomerases in yeast. Front Biosci. 2004; 9 : 2420–2446. doi: 10.2741/1405 15353296.

17. Dolinski K, Muir S, Cardenas M, Heitman J. All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997; 94(24):13093–13098. doi: 10.1073/pnas.94.24.13093 9371805.

18. Cameron AM, Nucifora FC Jr., Fung ET, Livingston DJ, Aldape RA, Ross CA, et al. FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400–1401) and anchors calcineurin to this FK506-like domain. J Biol Chem. 1997; 272(44):27582–27588. doi: 10.1074/jbc.272.44.27582 9346894.

19. Wang T, Donahoe PK, Zervos AS. Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science. 1994; 265(5172):674–676. doi: 10.1126/science.7518616 7518616.

20. Chen YG, Liu F, Massague J. Mechanism of TGFbeta receptor inhibition by FKBP12. EMBO J. 1997; 16(13):3866–3876. doi: 10.1093/emboj/16.13.3866 9233797.

21. Yang WM, Inouye CJ, Seto E. Cyclophilin A and FKBP12 interact with YY1 and alter its transcriptional activity. J Biol Chem. 1995; 270(25):15187–15193. doi: 10.1074/jbc.270.25.15187 7541038.

22. Ahearn IM, Tsai FD, Court H, Zhou M, Jennings BC, Ahmed M, et al. FKBP12 binds to acylated H-ras and promotes depalmitoylation. Mol Cell. 2011; 41(2):173–185. doi: 10.1016/j.molcel.2011.01.001 21255728.

23. Hemenway CS, Heitman J. Immunosuppressant target protein FKBP12 is required for P-glycoprotein function in yeast. J Biol Chem. 1996; 271(31):18527–18534. doi: 10.1074/jbc.271.31.18527 8702500.

24. Alarcon CM, Heitman J. FKBP12 physically and functionally interacts with aspartokinase in Saccharomyces cerevisiae. Mol Cell Biol. 1997; 17(10):5968–5975. doi: 10.1128/mcb.17.10.5968 9315655.

25. Arevalo-Rodriguez M, Pan X, Boeke JD, Heitman J. FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent toxic intermediate accumulation. Eukaryot Cell. 2004; 3(5):1287–1296. doi: 10.1128/EC.3.5.1287-1296.2004 15470257.

26. Dolinski KJ, Heitman J. Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase. Genetics. 1999; 151(3):935–944. 10049913.

27. Berger AB, Decourty L, Badis G, Nehrbass U, Jacquier A, Gadal O. Hmo1 is required for TOR-dependent regulation of ribosomal protein gene transcription. Mol Cell Biol. 2007; 27(22):8015–8026. doi: 10.1128/MCB.01102-07 17875934.

28. Knight B, Kubik S, Ghosh B, Bruzzone MJ, Geertz M, Martin V, et al. Two distinct promoter architectures centered on dynamic nucleosomes control ribosomal protein gene transcription. Genes Dev. 2014; 28(15):1695–1709. doi: 10.1101/gad.244434.114 25085421.

29. Kasahara K, Ki S, Aoyama K, Takahashi H, Kokubo T. Saccharomyces cerevisiae HMO1 interacts with TFIID and participates in start site selection by RNA polymerase II. Nucleic Acids Res. 2008; 36(4):1343–1357. https://doi.org/gkm1068 [pii] doi: 10.1093/nar/gkm1068 18187511.

30. Reja R, Vinayachandran V, Ghosh S, Pugh BF. Molecular mechanisms of ribosomal protein gene coregulation. Genes Dev. 2015; 29(18):1942–1954. doi: 10.1101/gad.268896.115 26385964.

31. Hall DB, Wade JT, Struhl K. An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae. Mol Cell Biol. 2006; 26(9):3672–3679. doi: 10.1128/MCB.26.9.3672-3679.2006 16612005.

32. Kasahara K, Ohtsuki K, Ki S, Aoyama K, Takahashi H, Kobayashi T, et al. Assembly of regulatory factors on rRNA and ribosomal protein genes in Saccharomyces cerevisiae. Mol Cell Biol. 2007; 27(19):6686–6705. https://doi.org/MCB.00876-07 [pii] doi: 10.1128/MCB.00876-07 17646381.

33. Kasahara K, Ohyama Y, Kokubo T. Hmo1 directs pre-initiation complex assembly to an appropriate site on its target gene promoters by masking a nucleosome-free region. Nucleic Acids Res. 2011; 39(10):4136–4150. https://doi.org/gkq1334 [pii] doi: 10.1093/nar/gkq1334 21288884.

34. Murugesapillai D, McCauley MJ, Huo R, Nelson Holte MH, Stepanyants A, Maher LJ 3rd, et al. DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome-free chromatin. Nucleic Acids Res. 2014; 42(14):8996–9004. doi: 10.1093/nar/gku635 25063301.

35. Hepp MI, Alarcon V, Dutta A, Workman JL, Gutierrez JL. Nucleosome remodeling by the SWI/SNF complex is enhanced by yeast high mobility group box (HMGB) proteins. Biochim Biophys Acta. 2014; 1839(9):764–772. doi: 10.1016/j.bbagrm.2014.06.014 24972368.

36. Lieb JD, Liu X, Botstein D, Brown PO. Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nat Genet. 2001; 28(4):327–334. doi: 10.1038/ng569 11455386.

37. Wade JT, Hall DB, Struhl K. The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes. Nature. 2004; 432(7020):1054–1058. doi: 10.1038/nature03175 15616568.

38. Kasahara K, Higashino A, Unzai S, Yoshikawa H, Kokubo T. Oligomerization of Hmo1 mediated by box A is essential for DNA binding in vitro and in vivo. Genes Cells. 2016; 21(12):1333–1352. doi: 10.1111/gtc.12449 27860073.

39. Martin DE, Soulard A, Hall MN. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell. 2004; 119(7):969–979. doi: 10.1016/j.cell.2004.11.047 15620355.

40. Nishimura K, Kanemaki MT. Rapid Depletion of Budding Yeast Proteins via the Fusion of an Auxin-Inducible Degron (AID). Curr Protoc Cell Biol. 2014; 64 : 20 29 21–16. doi: 10.1002/0471143030.cb2009s64 25181302.

41. Rudra D, Zhao Y, Warner JR. Central role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteins. EMBO J. 2005; 24(3):533–542. doi: 10.1038/sj.emboj.7600553 15692568.

42. Schawalder SB, Kabani M, Howald I, Choudhury U, Werner M, Shore D. Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. Nature. 2004; 432(7020):1058–1061. doi: 10.1038/nature03200 15616569.

43. Papai G, Tripathi MK, Ruhlmann C, Layer JH, Weil PA, Schultz P. TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation. Nature. 2010; 465(7300):956–960. doi: 10.1038/nature09080 20559389.

44. Koser PL, Eng WK, Bossard MJ, McLaughlin MM, Cafferkey R, Sathe GM, et al. The tyrosine89 residue of yeast FKBP12 is required for rapamycin binding. Gene. 1993; 129(2):159–165. doi: 10.1016/0378-1119(93)90264-4 8325502.

45. Lorenz MC, Heitman J. TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin. J Biol Chem. 1995; 270(46):27531–27537. doi: 10.1074/jbc.270.46.27531 7499212.

46. Millson SH, Piper PW. Insights from yeast into whether the inhibition of heat shock transcription factor (Hsf1) by rapamycin can prevent the Hsf1 activation that results from treatment with an Hsp90 inhibitor. Oncotarget. 2014; 5(13):5054–5064. doi: 10.18632/oncotarget.2077 24970820.

47. Wiederrecht G, Hung S, Chan HK, Marcy A, Martin M, Calaycay J, et al. Characterization of high molecular weight FK-506 binding activities reveals a novel FK-506-binding protein as well as a protein complex. J Biol Chem. 1992; 267(30):21753–21760. 1383226.

48. Van Duyne GD, Standaert RF, Karplus PA, Schreiber SL, Clardy J. Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin. J Mol Biol. 1993; 229(1):105–124. doi: 10.1006/jmbi.1993.1012 7678431.

49. Michnick SW, Rosen MK, Wandless TJ, Karplus M, Schreiber SL. Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin. Science. 1991; 252(5007):836–839. doi: 10.1126/science.1709301 1709301.

50. Kunz J, Loeschmann A, Deuter-Reinhard M, Hall MN. FAP1, a homologue of human transcription factor NF-X1, competes with rapamycin for binding to FKBP12 in yeast. Mol Microbiol. 2000; 37(6):1480–1493. https://doi.org/mmi2105 [pii]. doi: 10.1046/j.1365-2958.2000.02105.x 10998178.

51. Pina B, Fernandez-Larrea J, Garcia-Reyero N, Idrissi FZ. The different (sur)faces of Rap1p. Mol Genet Genomics. 2003; 268(6):791–798. doi: 10.1007/s00438-002-0801-3 12655405.

52. Idrissi FZ, Fernandez-Larrea JB, Pina B. Structural and functional heterogeneity of Rap1p complexes with telomeric and UASrpg-like DNA sequences. J Mol Biol. 1998; 284(4):925–935. doi: 10.1006/jmbi.1998.2215 9837716.

53. Wotton D, Shore D. A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev. 1997; 11(6):748–760. doi: 10.1101/gad.11.6.748 9087429.

54. Kyrion G, Liu K, Liu C, Lustig AJ. RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev. 1993; 7(7A):1146–1159. doi: 10.1101/gad.7.7a.1146 8319907.

55. Moretti P, Freeman K, Coodly L, Shore D. Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes Dev. 1994; 8(19):2257–2269. doi: 10.1101/gad.8.19.2257 7958893.

56. Mizuno T, Kishimoto T, Shinzato T, Haw R, Chambers A, Wood J, et al. Role of the N-terminal region of Rap1p in the transcriptional activation of glycolytic genes in Saccharomyces cerevisiae. Yeast. 2004; 21(10):851–866. doi: 10.1002/yea.1123 15300680.

57. Lopez MC, Smerage JB, Baker HV. Multiple domains of repressor activator protein 1 contribute to facilitated binding of glycolysis regulatory protein 1. Proc Natl Acad Sci U S A. 1998; 95(24):14112–14117. doi: 10.1073/pnas.95.24.14112 9826662.

58. Schmid M, Durussel T, Laemmli UK. ChIC and ChEC; genomic mapping of chromatin proteins. Mol Cell. 2004; 16(1):147–157. doi: 10.1016/j.molcel.2004.09.007 15469830.

59. Zentner GE, Kasinathan S, Xin B, Rohs R, Henikoff S. ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo. Nat Commun. 2015; 6 : 8733. doi: 10.1038/ncomms9733 26490019.

60. Cardenas ME, Heitman J. FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. EMBO J. 1995; 14(23):5892–5907. 8846782.

61. Timmers HTM, Tora L. Transcript Buffering: A Balancing Act between mRNA Synthesis and mRNA Degradation. Mol Cell. 2018; 72(1):10–17. doi: 10.1016/j.molcel.2018.08.023 30290147.

62. Sun M, Schwalb B, Schulz D, Pirkl N, Etzold S, Lariviere L, et al. Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation. Genome Res. 2012; 22(7):1350–1359. doi: 10.1101/gr.130161.111 22466169.

63. Quinlan AR. BEDTools: The Swiss-Army Tool for Genome Feature Analysis. Curr Protoc Bioinformatics. 2014; 47 : 11 12 11–34. doi: 10.1002/0471250953.bi1112s47 25199790.

64. Kushnirov VV. Rapid and reliable protein extraction from yeast. Yeast. 2000; 16(9):857–860. https://doi.org/10.1002/1097-0061(20000630)16 : 9<857::AID-YEA561>3.0.CO;2-B. 10861908.

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