Drosophila RpS12 controls translation, growth, and cell competition through Xrp1

English version

Autoři: Zhejun Ji ^aff001; Marianthi Kiparaki ^aff001; Virginia Folgado ^aff001; Amit Kumar ^aff001; Jorge Blanco ^aff001; Gerard Rimesso ^aff001; Jacky Chuen ^aff001; Yang Liu ^aff001; Deyou Zheng ^aff001; Nicholas E. Baker ^aff001
Působiště autorů: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America ^aff001; The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, United States of America ^aff002; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America ^aff003; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America ^aff004; Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, United States of America ^aff005
Vyšlo v časopise: Drosophila RpS12 controls translation, growth, and cell competition through Xrp1. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008513
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008513

Souhrn

Whereas complete loss of Rp function is generally lethal, most heterozygous Rp mutants grow more slowly and are subject to competitive loss from mosaics tissues that also contain wild type cells. The rpS12 gene has a special role in the cell competition of other Ribosomal Protein (Rp) mutant cells in Drosophila. Elimination by cell competition is promoted by higher RpS12 levels and prevented by a specific rpS12 mis-sense mutation, identifying RpS12 as a key effector of cell competition due to mutations in other Rp genes. Here we show that RpS12 is also required for other aspects of Rp mutant phenotypes, including hundreds of gene expression changes that occur in ‘Minute’ Rp heterozygous wing imaginal discs, overall translation rate, and the overall rate of organismal development, all through the bZip protein Xrp1 that is one of the RpS12-regulated genes. Our findings outline the regulatory response to mutations affecting essential Rp genes that controls overall translation, growth, and cell competition, and which may contribute to cancer and other diseases.

Klíčová slova:

Gene expression – Gene regulation – Imaginal discs – Messenger RNA – Point mutation – Protein translation – Ribosomes

Zdroje

1. de la Cruz J, Karbstein K, Woolford JL, Jr. Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo. Annu Rev Biochem. 2015;84 : 93–129. doi: 10.1146/annurev-biochem-060614-033917 25706898; PubMed Central PMCID: PMC4772166.

2. Warner JR, McIntosh KB. How common are extraribosomal functions of ribosomal proteins? Mol Cell. 2009;34(1):3–11. doi: 10.1016/j.molcel.2009.03.006 19362532; PubMed Central PMCID: PMC2679180.

3. Zhou X, Liao WJ, Liao JM, Liao P, Lu H. Ribosomal proteins: functions beyond the ribosome. J Mol Cell Biol. 2015;7(2):92–104. doi: 10.1093/jmcb/mjv014 25735597; PubMed Central PMCID: PMC4481666.

4. Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM. Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood. 2012;119(16):3815–9. Epub 2012/03/01. doi: 10.1182/blood-2011-08-375972 blood-2011-08-375972 [pii]. 22362038; PubMed Central PMCID: PMC3335385.

5. De Keersmaecker K, Sulima SO, Dinman JD. Ribosomopathies and the paradox of cellular hypo -⁠ to hyperproliferation. Blood. 2015;125(9):1377–82. doi: 10.1182/blood-2014-10-569616 25575543; PubMed Central PMCID: PMC4342353.

6. Sulima SO, Hofman IJF, De Keersmaecker K, Dinman JD. How Ribosomes Translate Cancer. Cancer Discov. 2017;7(10):1069–87. doi: 10.1158/2159-8290.CD-17-0550 28923911; PubMed Central PMCID: PMC5630089.

7. Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, et al. The Genetic Landscape of Diamond-Blackfan Anemia. Am J Hum Genet. 2018;103(6):930–47. doi: 10.1016/j.ajhg.2018.10.027 30503522; PubMed Central PMCID: PMC6288280.

8. Marygold SJ, Roote J, Reuter G, Lambertsson A, Ashburner M, Millburn GH, et al. The ribosomal protein genes and Minute loci of Drosophila melanogaster. Genome Biol. 2007;8(10):R216. Epub 2007/10/12. doi: 10.1186/gb-2007-8-10-r216 17927810; PubMed Central PMCID: PMC2246290.

9. Lambertsson A. The Minute genes in Drosophila and their molecular functions. Advances in Genetics. 1998;38 : 69–134. doi: 10.1016/s0065-2660(08)60142-x 9677706

10. Morata G, Ripoll P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Developmental Biology. 1975;42 : 211–21. doi: 10.1016/0012-1606(75)90330-9 1116643

11. Claveria C, Torres M. Cell Competition: Mechanisms and Physiological Roles. Annu Rev Cell Dev Biol. 2016;32 : 411–39. doi: 10.1146/annurev-cellbio-111315-125142 27501445.

12. Baker NE. Mechanisms of cell competition emerging from Drosophila studies. Curr Opin Cell Biol. 2017;48 : 40–6. doi: 10.1016/j.ceb.2017.05.002 28600967.

13. Lee CH, Rimesso G, Reynolds DM, Cai J, Baker NE. Whole-Genome Sequencing and iPLEX MassARRAY Genotyping Map an EMS-Induced Mutation Affecting Cell Competition in Drosophila melanogaster. G3 (Bethesda). 2016;6(10):3207–17. doi: 10.1534/g3.116.029421 27574103; PubMed Central PMCID: PMC5068942.

14. Baillon L, Germani F, Rockel C, Hilchenbach J, Basler K. Xrp1 is a transcription factor required for cell competition-driven elimination of loser cells. Sci Rep. 2018;8(1):17712. doi: 10.1038/s41598-018-36277-4 30531963; PubMed Central PMCID: PMC6286310.

15. Tyler DM, Li W, Zhuo N, Pellock B, Baker NE. Genes affecting cell competition in Drosophila. Genetics. 2007;175(2):643–57. Epub 2006/11/18. genetics.106.061929 [pii] doi: 10.1534/genetics.106.061929 17110495; PubMed Central PMCID: PMC1800612.

16. Lee CH, Kiparaki M, Blanco J, Folgado V, Ji Z, Kumar A, et al. A Regulatory Response to Ribosomal Protein Mutations Controls Translation, Growth, and Cell Competition. Dev Cell. 2018;46(4):456–69 e4. doi: 10.1016/j.devcel.2018.07.003 30078730; PubMed Central PMCID: PMC6261318.

17. Francis MJ, Roche S, Cho MJ, Beall E, Min B, Panganiban RP, et al. Drosophila IRBP bZIP heterodimer binds P-element DNA and affects hybrid dysgenesis. Proc Natl Acad Sci U S A. 2016;113(46):13003–8. doi: 10.1073/pnas.1613508113 27799520; PubMed Central PMCID: PMC5135294.

18. Mallik M, Catinozzi M, Hug CB, Zhang L, Wagner M, Bussmann J, et al. Xrp1 genetically interacts with the ALS-associated FUS orthologue caz and mediates its toxicity. J Cell Biol. 2018. doi: 10.1083/jcb.201802151 30209068.

19. Brodsky MH, Weinert BT, Tsang G, Rong YS, McGinnis NM, Golic KG, et al. Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol Cell Biol. 2004;24(3):1219–31. Epub 2004/01/20. doi: 10.1128/MCB.24.3.1219-1231.2004 14729967; PubMed Central PMCID: PMC321428.

20. Akdemir F, Christich A, Sogame N, Chapo J, Abrams JM. p53 directs focused genomic responses in Drosophila. Oncogene. 2007;26(36):5184–93. Epub 2007/02/22. doi: 10.1038/sj.onc.1210328 17310982.

21. Boulan L, Andersen D, Colombani J, Boone E, Leopold P. Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila. Dev Cell. 2019;49(5):811–8 e4. doi: 10.1016/j.devcel.2019.03.016 31006647.

22. Kucinski I, Dinan M, Kolahgar G, Piddini E. Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status. Nat Commun. 2017;8(1):136. doi: 10.1038/s41467-017-00145-y 28743877.

23. Kale A, Ji Z, Kiparaki M, Blanco J, Rimesso G, Flibotte S, et al. Ribosomal Protein S12e Has a Distinct Function in Cell Competition. Dev Cell. 2018;44(1):42–55 e4. doi: 10.1016/j.devcel.2017.12.007 29316439; PubMed Central PMCID: PMC5784854.

24. Lee CH, Kiparaki M, Blanco J, Folgado V, Ji Z, Kumar A, et al. A Regulatory Response to Ribosomal Protein Mutations Controls Translation, Growth, and Cell Competition. Dev Cell. 2018;46 : 456–69. doi: 10.1016/j.devcel.2018.07.003 30078730.

25. Moreno E, Basler K, Morata G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature. 2002;416 : 755–9. doi: 10.1038/416755a 11961558

26. Akai N, Igaki T, Ohsawa S. Wingless signaling regulates winner/loser status in Minute cellcmpetition. Genes Cells. 2018;23(3):234–40. doi: 10.1111/gtc.12568 29431244.

27. Moullan N, Mouchiroud L, Wang X, Ryu D, Williams EG, Mottis A, et al. Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research. Cell Rep. 2015. doi: 10.1016/j.celrep.2015.02.034 25772356; PubMed Central PMCID: PMC4565776.

28. Mortison JD, Schenone M, Myers JA, Zhang Z, Chen L, Ciarlo C, et al. Tetracyclines Modify Translation by Targeting Key Human rRNA Substructures. Cell Chem Biol. 2018;25(12):1506–18 e13. doi: 10.1016/j.chembiol.2018.09.010 30318461; PubMed Central PMCID: PMC6309532.

29. Merino MM, Rhiner C, Lopez-Gay JM, Buechel D, Hauert B, Moreno E. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell. 2015;160(3):461–76. Epub 2015/01/21. doi: 10.1016/j.cell.2014.12.017 25601460; PubMed Central PMCID: PMC4313366.

30. Warren AJ. Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome. Adv Biol Regul. 2018;67 : 109–27. doi: 10.1016/j.jbior.2017.09.002 28942353.

31. Weis F, Giudice E, Churcher M, Jin L, Hilcenko C, Wong CC, et al. Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Nat Struct Mol Biol. 2015;22(11):914–9. doi: 10.1038/nsmb.3112 26479198; PubMed Central PMCID: PMC4871238.

32. Miluzio A, Ricciardi S, Manfrini N, Alfieri R, Oliveto S, Brina D, et al. Translational control by mTOR-independent routes: how eIF6 organizes metabolism. Biochem Soc Trans. 2016;44(6):1667–73. doi: 10.1042/BST20160179 27913676.

33. Deisenroth C, Franklin DA, Zhang Y. The Evolution of the Ribosomal Protein-MDM2-p53 Pathway. Cold Spring Harb Perspect Med. 2016;6(12). doi: 10.1101/cshperspect.a026138 27908926.

34. Donati G, Peddigari S, Mercer CA, Thomas G. 5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint. Cell Rep. 2013;4(1):87–98. doi: 10.1016/j.celrep.2013.05.045 23831031; PubMed Central PMCID: PMC3928573.

35. Raiser DM, Narla A, Ebert BL. The emerging importance of ribosomal dysfunction in the pathogenesis of hematologic disorders. Leukemia & lymphoma. 2014;55(3):491–500. Epub 2013/07/19. doi: 10.3109/10428194.2013.812786 23863123.

36. Danilova N, Gazda HT. Ribosomopathies: how a common root can cause a tree of pathologies. Dis Model Mech. 2015;8(9):1013–26. doi: 10.1242/dmm.020529 26398160; PubMed Central PMCID: PMC4582105.

37. Ellis SR. Nucleolar stress in Diamond Blackfan anemia pathophysiology. Biochim Biophys Acta. 2014;1842(6):765–8. doi: 10.1016/j.bbadis.2013.12.013 24412987.

38. Khajuria RK, Munschauer M, Ulirsch JC, Fiorini C, Ludwig LS, McFarland SK, et al. Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis. Cell. 2018;173(1):90–103 e19. doi: 10.1016/j.cell.2018.02.036 29551269; PubMed Central PMCID: PMC5866246.

39. Mills EW, Green R. Ribosomopathies: There's strength in numbers. Science. 2017;358(6363). doi: 10.1126/science.aan2755 29097519.

40. Derenzini E, Agostinelli C, Rossi A, Rossi M, Scellato F, Melle F, et al. Genomic alterations of ribosomal protein genes in diffuse large B cell lymphoma. Br J Haematol. 2019;185(2):330–4. doi: 10.1111/bjh.15442 29911350.

41. Vincent J, Girdham C, O'Farrell P. A cell-autonomous, ubiquitous marker for the analysis of Drosophila genetic mosaics. Developmental Biology. 1994;164 : 328–31. doi: 10.1006/dbio.1994.1203 8026635

42. Janody F, Lee JD, Jahren N, Hazelett DJ, Benlali A, Miura GI, et al. A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development. Genetics. 2004;166(1):187–200. doi: 10.1534/genetics.166.1.187 15020417.

43. Burke R, Basler K. Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development. 1996;122 : 2261–9. 8681806

44. Golic KG. Site-specific recombination between homologous chromosomes in Drosophila. Science. 1991;252 : 958–61. doi: 10.1126/science.2035025 2035025

45. Xu T, Rubin GM. Analysis of genetic mosaics in the developing and adult Drosophila tissues. Development. 1993;117 : 1223–36. 8404527

46. Newsome TP, Asling B, Dickson BJ. Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development. 2000;127 : 851–60. 10648243

47. Sullivan W, Ashburner M, Hawley RS. Drosophila protocols: Cold Spring Harbor Laboratory Press; 2000.

48. Sultan R, Stampas A, Goldberg MB, Baker NE. Drug resistance of bacteria commensal with Drosophila melanogaster in laboratory cultures. Drosoph Inf Serv. 2001;84(December 2001):176–80.

49. Baker NE, Li K, Quiquand M, Ruggiero R, Wang LH. Eye development. Methods. 2014;68(1):252–9. doi: 10.1016/j.ymeth.2014.04.007 24784530; PubMed Central PMCID: PMC4073679.

50. Sanchez CG, Teixeira FK, Czech B, Preall JB, Zamparini AL, Seifert JR, et al. Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation. Cell Stem Cell. 2016;18(2):276–90. doi: 10.1016/j.stem.2015.11.004 26669894; PubMed Central PMCID: PMC4744108.

51. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi: 10.1186/s13059-014-0550-8 25516281; PubMed Central PMCID: PMC4302049.

52. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25(1):25–9. doi: 10.1038/75556 10802651; PubMed Central PMCID: PMC3037419.

53. Mi H, Huang X, Muruganujan A, Tang H, Mills C, Kang D, et al. PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res. 2017;45(D1):D183–D9. doi: 10.1093/nar/gkw1138 27899595; PubMed Central PMCID: PMC5210595.

54. The Gene Ontology C. Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res. 2017;45(D1):D331–D8. doi: 10.1093/nar/gkw1108 27899567; PubMed Central PMCID: PMC5210579.

55. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9 : 559. doi: 10.1186/1471-2105-9-559 19114008; PubMed Central PMCID: PMC2631488.

56. Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. 2005;4:Article17. doi: 10.2202/1544-6115.1128 16646834.

57. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. doi: 10.1093/nar/gkv007 25605792; PubMed Central PMCID: PMC4402510.

58. Romero-Pozuelo J, Demetriades C, Schroeder P, Teleman AA. CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc. Dev Cell. 2017;42(4):376–87 e5. doi: 10.1016/j.devcel.2017.07.019 28829945.