#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Ribosomal Protein Rpl22 Controls Ribosome Composition by Directly Repressing Expression of Its Own Paralog, Rpl22l1


Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22−/− mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22−/− mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1) expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.


Vyšlo v časopise: The Ribosomal Protein Rpl22 Controls Ribosome Composition by Directly Repressing Expression of Its Own Paralog, Rpl22l1. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003708
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003708

Souhrn

Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22−/− mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22−/− mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1) expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.


Zdroje

1. PlantaRJ (1997) Regulation of ribosome synthesis in yeast. Yeast 13: 1505–1518.

2. RudraD, WarnerJR (2004) What better measure than ribosome synthesis? Genes Dev 18: 2431–2436.

3. LaferteA, FavryE, SentenacA, RivaM, CarlesC, et al. (2006) The transcriptional activity of RNA polymerase I is a key determinant for the level of all ribosome components. Genes Dev 20: 2030–2040.

4. Fromont-RacineM, SengerB, SaveanuC, FasioloF (2003) Ribosome assembly in eukaryotes. Gene 313: 17–42.

5. LiuJM, EllisSR (2006) Ribosomes and marrow failure: coincidental association or molecular paradigm? Blood 107: 4583–4588.

6. NarlaA, EbertBL (2010) Ribosomopathies: human disorders of ribosome dysfunction. Blood 115: 3196–3205.

7. ScheperGC, van der KnaapMS, ProudCG (2007) Translation matters: protein synthesis defects in inherited disease. Nat Rev Genet 8: 711–723.

8. EllisSR, LiptonJM (2008) Diamond Blackfan anemia: a disorder of red blood cell development. Curr Top Dev Biol 82: 217–241.

9. CmejlaR, CmejlovaJ, HandrkovaH, PetrakJ, PospisilovaD (2007) Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat 28: 1178–1182.

10. SteffenKK, MacKayVL, KerrEO, TsuchiyaM, HuD, et al. (2008) Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell 133: 292–302.

11. ChiocchettiA, ZhouJ, ZhuH, KarlT, HaubenreisserO, et al. (2007) Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life span. Exp Gerontol 42: 275–286.

12. HansenM, TaubertS, CrawfordD, LibinaN, LeeSJ, et al. (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6: 95–110.

13. KaeberleinM, PowersRW (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193–1196.

14. BrodersenDE, NissenP (2005) The social life of ribosomal proteins. Febs J 272: 2098–2108.

15. NollerHF, HoffarthV, ZimniakL (1992) Unusual resistance of peptidyl transferase to protein extraction procedures. Science 256: 1416–1419.

16. WoolIG (1996) Extraribosomal functions of ribosomal proteins. Trends Biochem Sci 21: 164–165.

17. WarnerJR, McIntoshKB (2009) How common are extraribosomal functions of ribosomal proteins? Molecular cell 34: 3–11.

18. BhavsarRB, MakleyLN, TsonisPA (2010) The other lives of ribosomal proteins. Human genomics 4: 327–344.

19. VilardellJ, WarnerJR (1994) Regulation of splicing at an intermediate step in the formation of the spliceosome. Genes & development 8: 211–220.

20. MaciasS, BragulatM, TardiffDF, VilardellJ (2008) L30 binds the nascent RPL30 transcript to repress U2 snRNP recruitment. Molecular cell 30: 732–742.

21. MalyginAA, ParakhnevitchNM, IvanovAV, EperonIC, KarpovaGG (2007) Human ribosomal protein S13 regulates expression of its own gene at the splicing step by a feedback mechanism. Nucleic acids research 35: 6414–6423.

22. MatssonH, DaveyEJ, DraptchinskaiaN, HamaguchiI, OokaA, et al. (2004) Targeted disruption of the ribosomal protein S19 gene is lethal prior to implantation. Mol Cell Biol 24: 4032–4037.

23. OliverER, SaundersTL, TarleSA, GlaserT (2004) Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131: 3907–3920.

24. TangQ, RiceDS, GoldowitzD (1999) Disrupted retinal development in the embryonic belly spot and tail mutant mouse. Developmental biology 207: 239–255.

25. RuvinskyI, SharonN, LererT, CohenH, Stolovich-RainM, et al. (2005) Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes & development 19: 2199–2211.

26. VolarevicS, StewartMJ, LedermannB, ZilbermanF, TerraccianoL, et al. (2000) Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science 288: 2045–2047.

27. PanicL, TamarutS, Sticker-JantscheffM, BarkicM, SolterD, et al. (2006) Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation. Molecular and cellular biology 26: 8880–8891.

28. AndersonSJ, LauritsenJP, HartmanMG, FousheeAM, LefebvreJM, et al. (2007) Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity 26: 759–772.

29. Kirn-SafranCB, OristianDS, FochtRJ, ParkerSG, VivianJL, et al. (2007) Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29. Dev Dyn 236: 447–460.

30. WolfeKH, ShieldsDC (1997) Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387: 708–713.

31. RotenbergMO, MoritzM, WoolfordJLJr (1988) Depletion of Saccharomyces cerevisiae ribosomal protein L16 causes a decrease in 60S ribosomal subunits and formation of half-mer polyribosomes. Genes Dev 2: 160–172.

32. DeanEJ, DavisJC, DavisRW, PetrovDA (2008) Pervasive and persistent redundancy among duplicated genes in yeast. PLoS genetics 4: e1000113.

33. Baudin-BaillieuA, TollerveyD, CullinC, LacrouteF (1997) Functional analysis of Rrp7p, an essential yeast protein involved in pre-rRNA processing and ribosome assembly. Mol Cell Biol 17: 5023–5032.

34. HaarerB, ViggianoS, HibbsMA, TroyanskayaOG, AmbergDC (2007) Modeling complex genetic interactions in a simple eukaryotic genome: actin displays a rich spectrum of complex haploinsufficiencies. Genes Dev 21: 148–159.

35. NiL, SnyderM (2001) A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. Mol Biol Cell 12: 2147–2170.

36. EnyenihiAH, SaundersWS (2003) Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics 163: 47–54.

37. SteffenKK, McCormickMA, PhamKM, MacKayVL, DelaneyJR, et al. (2012) Ribosome deficiency protects against ER stress in Saccharomyces cerevisiae. Genetics 191: 107–118.

38. KomiliS, FarnyNG, RothFP, SilverPA (2007) Functional specificity among ribosomal proteins regulates gene expression. Cell 131: 557–571.

39. CostanzoM, BaryshnikovaA, BellayJ, KimY, SpearED, et al. (2010) The genetic landscape of a cell. Science 327: 425–431.

40. Auger-BuendiaMA, LonguetM, TavitianA (1979) Kinetic studies on ribosomal proteins assembly in preribosomal particles and ribosomal subunits of mammalian cells. Biochim Biophys Acta 563: 113–128.

41. LavergneJP, ConquetF, ReboudJP, ReboudAM (1987) Role of acidic phosphoproteins in the partial reconstitution of the active 60 S ribosomal subunit. FEBS Lett 216: 83–88.

42. DobbelsteinM, ShenkT (1995) In vitro selection of RNA ligands for the ribosomal L22 protein associated with Epstein-Barr virus-expressed RNA by using randomized and cDNA-derived RNA libraries. J Virol 69: 8027–8034.

43. ToczyskiDP, MateraAG, WardDC, SteitzJA (1994) The Epstein-Barr virus (EBV) small RNA EBER1 binds and relocalizes ribosomal protein L22 in EBV-infected human B lymphocytes. Proc Natl Acad Sci U S A 91: 3463–3467.

44. LeS, SternglanzR, GreiderCW (2000) Identification of two RNA-binding proteins associated with human telomerase RNA. Mol Biol Cell 11: 999–1010.

45. RaoS, LeeSY, GutierrezA, PerrigoueJ, ThapaRJ, et al. (2012) Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120: 3764–3773.

46. FinakG, BertosN, PepinF, SadekovaS, SouleimanovaM, et al. (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nature medicine 14: 518–527.

47. BhattacharjeeA, RichardsWG, StauntonJ, LiC, MontiS, et al. (2001) Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proceedings of the National Academy of Sciences of the United States of America 98: 13790–13795.

48. BallifBA, CaoZ, SchwartzD, CarrawayKL (2006) Identification of 14-3-3epsilon substrates from embryonic murine brain. J Proteome Res 5: 2372–2379.

49. SugiharaY, HondaH, IidaT, MorinagaT, HinoS, et al. (2010) Proteomic analysis of rodent ribosomes revealed heterogeneity including ribosomal proteins L10-like, L22-like 1, and L39-like. Journal of proteome research 9: 1351–1366.

50. KeelSB, PhelpsS, SaboKM, O'LearyMN, Kirn-SafranCB, et al. (2012) Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis. Experimental hematology 40: 290–294.

51. GiaeverG, ChuAM, NiL, ConnellyC, RilesL, et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387–391.

52. BensaudeO (2011) Inhibiting eukaryotic transcription: Which compound to choose? How to evaluate its activity? Transcription 2: 103–108.

53. ToczyskiDP, SteitzJA (1993) The cellular RNA-binding protein EAP recognizes a conserved stem-loop in the Epstein-Barr virus small RNA EBER 1. Molecular and cellular biology 13: 703–710.

54. ZukerM (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic acids research 31: 3406–3415.

55. LiangH, LiWH (2009) Functional compensation by duplicated genes in mouse. Trends in genetics : TIG 25: 441–442.

56. FokV, Mitton-FryRM, GrechA, SteitzJA (2006) Multiple domains of EBER 1, an Epstein-Barr virus noncoding RNA, recruit human ribosomal protein L22. RNA 12: 872–882.

57. HoumaniJL, DavisCI, RufIK (2009) Growth-promoting properties of Epstein-Barr virus EBER-1 RNA correlate with ribosomal protein L22 binding. Journal of virology 83: 9844–9853.

58. ParenteauJ, DurandM, MorinG, GagnonJ, LucierJF, et al. (2011) Introns within ribosomal protein genes regulate the production and function of yeast ribosomes. Cell 147: 320–331.

59. NiJQ, LiuLP, HessD, RietdorfJ, SunFL (2006) Drosophila ribosomal proteins are associated with linker histone H1 and suppress gene transcription. Genes Dev 20: 1959–1973.

60. KimJ, ChubatsuLS, AdmonA, StahlJ, FellousR, et al. (1995) Implication of mammalian ribosomal protein S3 in the processing of DNA damage. The Journal of biological chemistry 270: 13620–13629.

61. KuhnJF, TranEJ, MaxwellES (2002) Archaeal ribosomal protein L7 is a functional homolog of the eukaryotic 15.5 kD/Snu13p snoRNP core protein. Nucleic acids research 30: 931–941.

62. MazumderB, SampathP, SeshadriV, MaitraRK, DiCorletoPE, et al. (2003) Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 115: 187–198.

63. ZhangY, DucAC, RaoS, SunXL, BilbeeAN, et al. (2013) Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs. Developmental cell 24: 411–425.

64. XueS, BarnaM (2012) Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nature reviews Molecular cell biology 13: 355–369.

65. KondrashovN, PusicA, StumpfCR, ShimizuK, HsiehAC, et al. (2011) Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145: 383–397.

66. ArmacheJP, JaraschA, AngerAM, VillaE, BeckerT, et al. (2010) Cryo-EM structure and rRNA model of a translating eukaryotic 80S ribosome at 5.5-A resolution. Proceedings of the National Academy of Sciences of the United States of America 107: 19748–19753.

67. ArmacheJP, JaraschA, AngerAM, VillaE, BeckerT, et al. (2010) Localization of eukaryote-specific ribosomal proteins in a 5.5-A cryo-EM map of the 80S eukaryotic ribosome. Proceedings of the National Academy of Sciences of the United States of America 107: 19754–19759.

68. MarygoldSJ, RooteJ, ReuterG, LambertssonA, AshburnerM, et al. (2007) The ribosomal protein genes and Minute loci of Drosophila melanogaster. Genome biology 8: R216.

69. WeijersD, Franke-van DijkM, VenckenRJ, QuintA, HooykaasP, et al. (2001) An Arabidopsis Minute-like phenotype caused by a semi-dominant mutation in a RIBOSOMAL PROTEIN S5 gene. Development 128: 4289–4299.

70. DegenhardtRF, Bonham-SmithPC (2008) Transcript profiling demonstrates absence of dosage compensation in Arabidopsis following loss of a single RPL23a paralog. Planta 228: 627–640.

71. WilliamsME, SussexIM (1995) Developmental regulation of ribosomal protein L16 genes in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 8: 65–76.

72. BortoluzziS, d'AlessiF, RomualdiC, DanieliGA (2001) Differential expression of genes coding for ribosomal proteins in different human tissues. Bioinformatics 17: 1152–1157.

73. MacKayVL, LiX, FloryMR, TurcottE, LawGL, et al. (2004) Gene expression analyzed by high-resolution state array analysis and quantitative proteomics: response of yeast to mating pheromone. Mol Cell Proteomics 3: 478–489.

74. KamijoT, ZindyF, RousselMF, QuelleDE, DowningJR, et al. (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91: 649–659.

75. TodaroGJ, GreenH (1963) Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. The Journal of cell biology 17: 299–313.

76. KimmelCB, BallardWW, KimmelSR, UllmannB, SchillingTF (1995) Stages of embryonic development of the zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 203: 253–310.

77. GiraldezAJ, MishimaY, RihelJ, GrocockRJ, Van DongenS, et al. (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312: 75–79.

78. StatonAA, KnautH, GiraldezAJ (2011) miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration. Nature genetics 43: 204–211.

79. MartinTE (1973) A simple general method to determine the proportion of active ribosomes in eukaryotic cells. Experimental cell research 80: 496–498.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 8
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#