Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes
Autoři:
Koji Ishikawa aff001; Akari Ishihara aff002; Hisao Moriya aff001
Působiště autorů:
Research Core for Interdisciplinary Sciences, Okayama University, Okayama, Japan
aff001; Course of Agrochemical Bioscience, Faculty of Agriculture, Okayama University, Okayama, Japan
aff002
Vyšlo v časopise:
Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009091
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009091
Souhrn
Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 12 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent stoichiometry control. Our study reveals the complexity and robustness of the stoichiometry control system.
Klíčová slova:
Control systems – Dosage compensation – Histones – Quality control – Ribonucleases – Stoichiometry – Ubiquitin ligases – Yeast
Zdroje
1. Zheng XY, O'Shea EK. Cyanobacteria Maintain Constant Protein Concentration despite Genome Copy-Number Variation. Cell Rep. 2017;19(3):497–504. doi: 10.1016/j.celrep.2017.03.067 28423314
2. Kafri M, Metzl-Raz E, Jona G, Barkai N. The Cost of Protein Production. Cell Rep. 2016;14(1):22–31. doi: 10.1016/j.celrep.2015.12.015 26725116
3. Dill KA, Ghosh K, Schmit JD. Physical limits of cells and proteomes. Proc Natl Acad Sci U S A. 2011;108(44):17876–82. doi: 10.1073/pnas.1114477108 22006304
4. Sopko R, Huang D, Preston N, Chua G, Papp B, Kafadar K, et al. Mapping pathways and phenotypes by systematic gene overexpression. Mol Cell. 2006;21(3):319–30. doi: 10.1016/j.molcel.2005.12.011 16455487
5. Makanae K, Kintaka R, Makino T, Kitano H, Moriya H. Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method. Genome research. 2013;23(2):300–11. doi: 10.1101/gr.146662.112 23275495
6. Moriya H. Quantitative nature of overexpression experiments. Mol Biol Cell. 2015;26(22):3932–9. doi: 10.1091/mbc.E15-07-0512 26543202
7. Ishikawa K, Makanae K, Iwasaki S, Ingolia NT, Moriya H. Post-Translational Dosage Compensation Buffers Genetic Perturbations to Stoichiometry of Protein Complexes. PLoS Genet. 2017;13(1):e1006554. doi: 10.1371/journal.pgen.1006554 28121980
8. Stingele S, Stoehr G, Peplowska K, Cox J, Mann M, Storchova Z. Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells. Molecular systems biology. 2012;8:608. doi: 10.1038/msb.2012.40 22968442
9. Dephoure N, Hwang S, O'Sullivan C, Dodgson SE, Gygi SP, Amon A, et al. Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast. eLife. 2014;3:e03023. doi: 10.7554/eLife.03023 25073701
10. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ, et al. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science (New York, NY). 2007;317(5840):916–24. doi: 10.1126/science.1142210 17702937
11. Shemorry A, Hwang CS, Varshavsky A. Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Mol Cell. 2013;50(4):540–51. doi: 10.1016/j.molcel.2013.03.018 23603116
12. Papp B, Pal C, Hurst LD. Dosage sensitivity and the evolution of gene families in yeast. Nature. 2003;424(6945):194–7. doi: 10.1038/nature01771 12853957
13. Li GW, Burkhardt D, Gross C, Weissman JS. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell. 2014;157(3):624–35. doi: 10.1016/j.cell.2014.02.033 24766808
14. Taggart JC, Li GW. Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes. Cell systems. 2018. doi: 10.1016/j.cels.2018.11.003 30553725
15. Ingolia NT, Hussmann JA, Weissman JS. Ribosome Profiling: Global Views of Translation. Cold Spring Harb Perspect Biol. 2018. doi: 10.1101/cshperspect.a032698 30037969
16. Sung MK, Reitsma JM, Sweredoski MJ, Hess S, Deshaies RJ. Ribosomal proteins produced in excess are degraded by the ubiquitin-proteasome system. Mol Biol Cell. 2016;27(17):2642–52. doi: 10.1091/mbc.E16-05-0290 27385339
17. Yanagitani K, Juszkiewicz S, Hegde RS. UBE2O is a quality control factor for orphans of multiprotein complexes. Science (New York, NY). 2017;357(6350):472–5. doi: 10.1126/science.aan0178 28774922
18. Hwang CS, Shemorry A, Varshavsky A. N-terminal acetylation of cellular proteins creates specific degradation signals. Science (New York, NY). 2010;327(5968):973–7. doi: 10.1126/science.1183147 20110468
19. Sung MK, Porras-Yakushi TR, Reitsma JM, Huber FM, Sweredoski MJ, Hoelz A, et al. A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins. eLife. 2016;5. doi: 10.7554/eLife.19105 27552055
20. Aksnes H, Ree R, Arnesen T. Co-translational, Post-translational, and Non-catalytic Roles of N-Terminal Acetyltransferases. Mol Cell. 2019;73(6):1097–114. doi: 10.1016/j.molcel.2019.02.007 30878283
21. Nguyen KT, Lee CS, Mun SH, Truong NT, Park SK, Hwang CS. N-terminal acetylation and the N-end rule pathway control degradation of the lipid droplet protein PLIN2. J Biol Chem. 2019;294(1):379–88. doi: 10.1074/jbc.RA118.005556 30425097
22. Varshavsky A. The N-end rule pathway and regulation by proteolysis. Protein Sci. 2011;20(8):1298–345. doi: 10.1002/pro.666 21633985
23. Harper JW, Bennett EJ. Proteome complexity and the forces that drive proteome imbalance. Nature. 2016;537(7620):328–38. doi: 10.1038/nature19947 27629639
24. Kats I, Khmelinskii A, Kschonsak M, Huber F, Kniess RA, Bartosik A, et al. Mapping Degradation Signals and Pathways in a Eukaryotic N-terminome. Mol Cell. 2018;70(3):488–501 e5. doi: 10.1016/j.molcel.2018.03.033 29727619
25. Gardner RG, Nelson ZW, Gottschling DE. Degradation-mediated protein quality control in the nucleus. Cell. 2005;120(6):803–15. doi: 10.1016/j.cell.2005.01.016 15797381
26. Bartel B, Wunning I, Varshavsky A. The recognition component of the N-end rule pathway. Embo j. 1990;9(10):3179–89. 2209542
27. Nguyen KT, Kim JM, Park SE, Hwang CS. N-terminal methionine excision of proteins creates tertiary destabilizing N-degrons of the Arg/N-end rule pathway. J Biol Chem. 2019;294(12):4464–76. doi: 10.1074/jbc.RA118.006913 30674553
28. Esakova O, Krasilnikov AS. Of proteins and RNA: the RNase P/MRP family. RNA. 2010;16(9):1725–47. doi: 10.1261/rna.2214510 20627997
29. Perederina A, Berezin I, Krasilnikov AS. In vitro reconstitution and analysis of eukaryotic RNase P RNPs. Nucleic Acids Res. 2018;46(13):6857–68. doi: 10.1093/nar/gky333 29722866
30. Dimitrova LN, Kuroha K, Tatematsu T, Inada T. Nascent peptide-dependent translation arrest leads to Not4p-mediated protein degradation by the proteasome. J Biol Chem. 2009;284(16):10343–52. doi: 10.1074/jbc.M808840200 19204001
31. Brandman O, Hegde RS. Ribosome-associated protein quality control. Nat Struct Mol Biol. 2016;23(1):7–15. doi: 10.1038/nsmb.3147 26733220
32. Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, et al. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell. 2012;151(5):1042–54. doi: 10.1016/j.cell.2012.10.044 23178123
33. Matsuo Y, Ikeuchi K, Saeki Y, Iwasaki S, Schmidt C, Udagawa T, et al. Ubiquitination of stalled ribosome triggers ribosome-associated quality control. Nat Commun. 2017;8(1):159. doi: 10.1038/s41467-017-00188-1 28757607
34. Perederina A, Esakova O, Koc H, Schmitt ME, Krasilnikov AS. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs. RNA. 2007;13(10):1648–55. doi: 10.1261/rna.654407 17717080
35. Perederina A, Esakova O, Quan C, Khanova E, Krasilnikov AS. Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain. Embo j. 2010;29(4):761–9. doi: 10.1038/emboj.2009.396 20075859
36. Aksnes H, Drazic A, Marie M, Arnesen T. First Things First: Vital Protein Marks by N-Terminal Acetyltransferases. Trends Biochem Sci. 2016;41(9):746–60. doi: 10.1016/j.tibs.2016.07.005 27498224
37. Magin RS, Liszczak GP, Marmorstein R. The molecular basis for histone H4- and H2A-specific amino-terminal acetylation by NatD. Structure. 2015;23(2):332–41. doi: 10.1016/j.str.2014.10.025 25619998
38. Song OK, Wang X, Waterborg JH, Sternglanz R. An Nalpha-acetyltransferase responsible for acetylation of the N-terminal residues of histones H4 and H2A. J Biol Chem. 2003;278(40):38109–12. doi: 10.1074/jbc.C300355200 12915400
39. Hole K, Van Damme P, Dalva M, Aksnes H, Glomnes N, Varhaug JE, et al. The human N-alpha-acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4. PLoS One. 2011;6(9):e24713. doi: 10.1371/journal.pone.0024713 21935442
40. Polevoda B, Hoskins J, Sherman F. Properties of Nat4, an N(alpha)-acetyltransferase of Saccharomyces cerevisiae that modifies N termini of histones H2A and H4. Mol Cell Biol. 2009;29(11):2913–24. doi: 10.1128/MCB.00147-08 19332560
41. Mullen JR, Kayne PS, Moerschell RP, Tsunasawa S, Gribskov M, Colavito-Shepanski M, et al. Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast. Embo j. 1989;8(7):2067–75. 2551674
42. Jiang Y, Rossi G, Ferro-Novick S. Bet2p and Mad2p are components of a prenyltransferase that adds geranylgeranyl onto Ypt1p and Sec4p. Nature. 1993;366(6450):84–6. doi: 10.1038/366084a0 8232542
43. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, et al. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012;109(31):12449–54. doi: 10.1073/pnas.1210303109 22814378
44. Eisenberg AR, Higdon A, Keskin A, Hodapp S, Jovanovic M, Brar GA. Precise Post-translational Tuning Occurs for Most Protein Complex Components during Meiosis. Cell Rep. 2018;25(13):3603–17.e2. doi: 10.1016/j.celrep.2018.12.008 30590036
45. Kim DH, Zhang W, Koepp DM. The Hect domain E3 ligase Tom1 and the F-box protein Dia2 control Cdc6 degradation in G1 phase. J Biol Chem. 2012;287(53):44212–20. doi: 10.1074/jbc.M112.401778 23129771
46. Singh RK, Kabbaj MH, Paik J, Gunjan A. Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis. Nat Cell Biol. 2009;11(8):925–33. doi: 10.1038/ncb1903 19578373
47. Iglesias N, Tutucci E, Gwizdek C, Vinciguerra P, Von Dach E, Corbett AH, et al. Ubiquitin-mediated mRNP dynamics and surveillance prior to budding yeast mRNA export. Genes Dev. 2010;24(17):1927–38. doi: 10.1101/gad.583310 20810649
48. Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, et al. Global analysis of protein localization in budding yeast. Nature. 2003;425(6959):686–91. doi: 10.1038/nature02026 14562095
49. Juszkiewicz S, Hegde RS. Quality Control of Orphaned Proteins. Mol Cell. 2018;71(3):443–57. doi: 10.1016/j.molcel.2018.07.001 30075143
50. Brennan CM, Vaites LP, Wells JN, Santaguida S, Paulo JA, Storchova Z, et al. Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells. Genes Dev. 2019. doi: 10.1101/gad.327494.119 31196865
51. Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, et al. NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation. PLoS Genet. 2011;7(7):e1002169. doi: 10.1371/journal.pgen.1002169 21750686
52. Osberg C, Aksnes H, Ninzima S, Marie M, Arnesen T. Microscopy-based Saccharomyces cerevisiae complementation model reveals functional conservation and redundancy of N-terminal acetyltransferases. Sci Rep. 2016;6:31627. doi: 10.1038/srep31627 27555049
53. Singh RK, Gonzalez M, Kabbaj MH, Gunjan A. Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae. PLoS One. 2012;7(5):e36295. doi: 10.1371/journal.pone.0036295 22570702
54. Kim HK, Kim RR, Oh JH, Cho H, Varshavsky A, Hwang CS. The N-terminal methionine of cellular proteins as a degradation signal. Cell. 2014;156(1–2):158–69. doi: 10.1016/j.cell.2013.11.031 24361105
55. Lemieux B, Laterreur N, Perederina A, Noel JF, Dubois ML, Krasilnikov AS, et al. Active Yeast Telomerase Shares Subunits with Ribonucleoproteins RNase P and RNase MRP. Cell. 2016;165(5):1171–81. doi: 10.1016/j.cell.2016.04.018 27156450
56. Diss G, Dube AK, Boutin J, Gagnon-Arsenault I, Landry CR. A systematic approach for the genetic dissection of protein complexes in living cells. Cell Rep. 2013;3(6):2155–67. doi: 10.1016/j.celrep.2013.05.004 23746448
57. Diss G, Gagnon-Arsenault I, Dion-Cote AM, Vignaud H, Ascencio DI, Berger CM, et al. Gene duplication can impart fragility, not robustness, in the yeast protein interaction network. Science (New York, NY). 2017;355(6325):630–4. doi: 10.1126/science.aai7685 28183979
58. Moriya H, Shimizu-Yoshida Y, Kitano H. In vivo robustness analysis of cell division cycle genes in Saccharomyces cerevisiae. PLoS Genet. 2006;2(7):e111. doi: 10.1371/journal.pgen.0020111 16839182
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