#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult Germ Line


Throughout adulthood, animal tissue homeostasis requires adult stem cell activities. A tight balance between self-renewal and differentiation protects against tissue overgrowth or loss. This balance is strongly influenced by niche-mediated signaling pathways that primarily trigger a transcriptional response in stem cells to promote self-renewal/proliferation. However, the cell-intrinsic mechanisms that modulate signaling pathways to promote proliferation or differentiation are poorly understood. Recently, post-transcriptional mRNA regulation emerged in diverse germline stem cell systems as an important gene expression mechanism, primarily preventing the protein synthesis of factors that promote the switch to differentiation. In the adult C. elegans germ line, this study finds that the evolutionarily conserved cytoplasmic poly(A) polymerase, GLD-4, plays an crucial role in maintaining a healthy balance between proliferation and differentiation forces. This is in part due to translational activation of the mRNA that encodes the germ cell-expressed Notch signaling receptor, an essential regulator of proliferation. Moreover, GLD-4 activity is part of a redundant genetic network downstream of Notch that, together with several other conserved mRNA regulators, promotes differentiation onset. Given the widespread expression of these conserved RNA regulators in metazoans, cell fate balances that are reinforced by translational activation and repression circuitries may therefore be a general mechanism of adult tissue maintenance.


Vyšlo v časopise: GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult Germ Line. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004647
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004647

Souhrn

Throughout adulthood, animal tissue homeostasis requires adult stem cell activities. A tight balance between self-renewal and differentiation protects against tissue overgrowth or loss. This balance is strongly influenced by niche-mediated signaling pathways that primarily trigger a transcriptional response in stem cells to promote self-renewal/proliferation. However, the cell-intrinsic mechanisms that modulate signaling pathways to promote proliferation or differentiation are poorly understood. Recently, post-transcriptional mRNA regulation emerged in diverse germline stem cell systems as an important gene expression mechanism, primarily preventing the protein synthesis of factors that promote the switch to differentiation. In the adult C. elegans germ line, this study finds that the evolutionarily conserved cytoplasmic poly(A) polymerase, GLD-4, plays an crucial role in maintaining a healthy balance between proliferation and differentiation forces. This is in part due to translational activation of the mRNA that encodes the germ cell-expressed Notch signaling receptor, an essential regulator of proliferation. Moreover, GLD-4 activity is part of a redundant genetic network downstream of Notch that, together with several other conserved mRNA regulators, promotes differentiation onset. Given the widespread expression of these conserved RNA regulators in metazoans, cell fate balances that are reinforced by translational activation and repression circuitries may therefore be a general mechanism of adult tissue maintenance.


Zdroje

1. KimbleJ (2011) Molecular regulation of the mitosis/meiosis decision in multicellular organisms. Cold Spring Harbor perspectives in biology 3: 1–16.

2. CrittendenSL, LeonhardKA, ByrdDT, KimbleJ (2006) Cellular analyses of the mitotic region in the Caenorhabditis elegans adult germ line. Molecular biology of the cell 17: 3051–3061.

3. MaciejowskiJ, UgelN, MishraB, IsopiM, HubbardEJ (2006) Quantitative analysis of germline mitosis in adult C. elegans. Developmental biology 292: 142–151.

4. FoxPM, VoughtVE, HanazawaM, LeeMH, MaineEM, et al. (2011) Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline. Development 138: 2223–2234.

5. CinquinO, CrittendenSL, MorganDE, KimbleJ (2010) Progression from a stem cell-like state to early differentiation in the C. elegans germ line. Proceedings of the National Academy of Sciences of the United States of America 107: 2048–2053.

6. HansenD, HubbardEJ, SchedlT (2004) Multi-pathway control of the proliferation versus meiotic development decision in the Caenorhabditis elegans germline. Developmental biology 268: 342–357.

7. EckmannCR, CrittendenSL, SuhN, KimbleJ (2004) GLD-3 and control of the mitosis/meiosis decision in the germline of Caenorhabditis elegans. Genetics 168: 147–160.

8. KimbleJE, WhiteJG (1981) On the control of germ cell development in Caenorhabditis elegans. Developmental biology 81: 208–219.

9. AustinJ, KimbleJ (1987) glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 51: 589–599.

10. ByrdDT, KimbleJ (2009) Scratching the niche that controls Caenorhabditis elegans germline stem cells. Seminars in cell & developmental biology 20: 1107–1113.

11. PepperAS, KillianDJ, HubbardEJ (2003) Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition. Genetics 163: 115–132.

12. BerryLW, WestlundB, SchedlT (1997) Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. Development 124: 925–936.

13. CrittendenSL, TroemelER, EvansTC, KimbleJ (1994) GLP-1 is localized to the mitotic region of the C. elegans germ line. Development 120: 2901–2911.

14. LamontLB, CrittendenSL, BernsteinD, WickensM, KimbleJ (2004) FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline. Developmental cell 7: 697–707.

15. LeeMH, HookB, PanG, KershnerAM, MerrittC, et al. (2007) Conserved regulation of MAP kinase expression by PUF RNA-binding proteins. PLoS genetics 3: e233.

16. KershnerAM, ShinH, HansenTJ, KimbleJ (2014) Discovery of two GLP-1/Notch target genes that account for the role of GLP-1/Notch signaling in stem cell maintenance. Proceedings of the National Academy of Sciences of the United States of America 111: 3739–3744.

17. LehmannR (2012) Germline stem cells: origin and destiny. Cell stem cell 10: 729–739.

18. CrittendenSL, BernsteinDS, BachorikJL, ThompsonBE, GallegosM, et al. (2002) A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature 417: 660–663.

19. KershnerAM, KimbleJ (2010) Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator. Proceedings of the National Academy of Sciences of the United States of America 107: 3936–3941.

20. MerrittC, SeydouxG (2010) The Puf RNA-binding proteins FBF-1 and FBF-2 inhibit the expression of synaptonemal complex proteins in germline stem cells. Development 137: 1787–1798.

21. CrittendenSL, EckmannCR, WangL, BernsteinDS, WickensM, et al. (2003) Regulation of the mitosis/meiosis decision in the Caenorhabditis elegans germline. Philosophical transactions of the Royal Society of London Series B, Biological sciences 358: 1359–1362.

22. JonesAR, SchedlT (1995) Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68. Genes & development 9: 1491–1504.

23. MarinVA, EvansTC (2003) Translational repression of a C. elegans Notch mRNA by the STAR/KH domain protein GLD-1. Development 130: 2623–2632.

24. RyderSP, FraterLA, AbramovitzDL, GoodwinEB, WilliamsonJR (2004) RNA target specificity of the STAR/GSG domain post-transcriptional regulatory protein GLD-1. Nature structural & molecular biology 11: 20–28.

25. WrightJE, GaidatzisD, SenftenM, FarleyBM, WesthofE, et al. (2011) A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1. The EMBO journal 30: 533–545.

26. HansenD, Wilson-BerryL, DangT, SchedlT (2004) Control of the proliferation versus meiotic development decision in the C. elegans germline through regulation of GLD-1 protein accumulation. Development 131: 93–104.

27. EckmannCR, KraemerB, WickensM, KimbleJ (2002) GLD-3, a Bicaudal-C homolog that inhibits FBF to control germline sex determination in C. elegans. Developmental cell 3: 697–710.

28. WangL, EckmannCR, KadykLC, WickensM, KimbleJ (2002) A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans. Nature 419: 312–316.

29. SuhN, JedamzikB, EckmannCR, WickensM, KimbleJ (2006) The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line. Proceedings of the National Academy of Sciences of the United States of America 103: 15108–15112.

30. SchmidM, KuchlerB, EckmannCR (2009) Two conserved regulatory cytoplasmic poly(A) polymerases, GLD-4 and GLD-2, regulate meiotic progression in C. elegans. Genes & development 23: 824–836.

31. MinasakiR, EckmannCR (2012) Subcellular specialization of multifaceted 3′end modifying nucleotidyltransferases. Current opinion in cell biology 24: 314–322.

32. SchmidtK, ButlerJS (2013) Nuclear RNA surveillance: role of TRAMP in controlling exosome specificity. Wiley interdisciplinary reviews RNA 4: 217–231.

33. RybarskaA, HarterinkM, JedamzikB, KupinskiAP, SchmidM, et al. (2009) GLS-1, a novel P granule component, modulates a network of conserved RNA regulators to influence germ cell fate decisions. PLoS genetics 5: e1000494.

34. HansenD, SchedlT (2013) Stem cell proliferation versus meiotic fate decision in Caenorhabditis elegans. Advances in experimental medicine and biology 757: 71–99.

35. KadykLC, KimbleJ (1998) Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development 125: 1803–1813.

36. OguraK, KishimotoN, MitaniS, Gengyo-AndoK, KoharaY (2003) Translational control of maternal glp-1 mRNA by POS-1 and its interacting protein SPN-4 in Caenorhabditis elegans. Development 130: 2495–2503.

37. NouschM, EckmannCR (2013) Translational control in the Caenorhabditis elegans germ line. Advances in experimental medicine and biology 757: 205–247.

38. EvansTC, CrittendenSL, KodoyianniV, KimbleJ (1994) Translational control of maternal glp-1 mRNA establishes an asymmetry in the C. elegans embryo. Cell 77: 183–194.

39. MaciejowskiJ, AhnJH, CiprianiPG, KillianDJ, ChaudharyAL, et al. (2005) Autosomal genes of autosomal/X-linked duplicated gene pairs and germ-line proliferation in Caenorhabditis elegans. Genetics 169: 1997–2011.

40. MinasakiR, RudelD, EckmannCR (2014) Increased sensitivity and accuracy of a single-stranded DNA splint-mediated ligation assay (sPAT) reveals poly(A) tail length dynamics of developmentally regulated mRNAs. RNA biology 11.

41. SuhN, CrittendenSL, GoldstrohmA, HookB, ThompsonB, et al. (2009) FBF and its dual control of gld-1 expression in the Caenorhabditis elegans germline. Genetics 181: 1249–1260.

42. LublinAL, EvansTC (2007) The RNA-binding proteins PUF-5, PUF-6, and PUF-7 reveal multiple systems for maternal mRNA regulation during C. elegans oogenesis. Developmental biology 303: 635–649.

43. HendzelMJ, WeiY, ManciniMA, Van HooserA, RanalliT, et al. (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106: 348–360.

44. JonesAR, FrancisR, SchedlT (1996) GLD-1, a cytoplasmic protein essential for oocyte differentiation, shows stage- and sex-specific expression during Caenorhabditis elegans germline development. Developmental biology 180: 165–183.

45. KalchhauserI, FarleyBM, PauliS, RyderSP, CioskR (2011) FBF represses the Cip/Kip cell-cycle inhibitor CKI-2 to promote self-renewal of germline stem cells in C. elegans. The EMBO journal 30: 3823–3829.

46. BiedermannB, WrightJ, SenftenM, KalchhauserI, SarathyG, et al. (2009) Translational repression of cyclin E prevents precocious mitosis and embryonic gene activation during C. elegans meiosis. Developmental cell 17: 355–364.

47. JeongJ, VerheydenJM, KimbleJ (2011) Cyclin E and Cdk2 control GLD-1, the mitosis/meiosis decision, and germline stem cells in Caenorhabditis elegans. PLoS genetics 7: e1001348.

48. KatohT, SakaguchiY, MiyauchiK, SuzukiT, KashiwabaraS, et al. (2009) Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes & development 23: 433–438.

49. HarrisRE, PargettM, SutcliffeC, UmulisD, AsheHL (2011) Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling. Developmental cell 20: 72–83.

50. InscoML, BaileyAS, KimJ, OlivaresGH, WapinskiOL, et al. (2012) A self-limiting switch based on translational control regulates the transition from proliferation to differentiation in an adult stem cell lineage. Cell stem cell 11: 689–700.

51. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.

52. VoroninaE, PaixA, SeydouxG (2012) The P granule component PGL-1 promotes the localization and silencing activity of the PUF protein FBF-2 in germline stem cells. Development 139: 3732–3740.

53. KamathRS, AhringerJ (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30: 313–321.

54. CowanCR, HymanAA (2006) Cyclin E-Cdk2 temporally regulates centrosome assembly and establishment of polarity in Caenorhabditis elegans embryos. Nature cell biology 8: 1441–1447.

55. ZhangB, GallegosM, PuotiA, DurkinE, FieldsS, et al. (1997) A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature 390: 477–484.

56. ZetkaMC, KawasakiI, StromeS, MullerF (1999) Synapsis and chiasma formation in Caenorhabditis elegans require HIM-3, a meiotic chromosome core component that functions in chromosome segregation. Genes & development 13: 2258–2270.

57. PenknerAM, FridkinA, GloggnitzerJ, BaudrimontA, MachacekT, et al. (2009) Meiotic chromosome homology search involves modifications of the nuclear envelope protein Matefin/SUN-1. Cell 139: 920–933.

58. GruidlME, SmithPA, KuznickiKA, McCroneJS, KirchnerJ, et al. (1996) Multiple potential germ-line helicases are components of the germ-line-specific P granules of Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America 93: 13837–13842.

59. PasierbekP, JantschM, MelcherM, SchleifferA, SchweizerD, et al. (2001) A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disjunction. Genes & development 15: 1349–1360.

60. BernsteinDS, ButerN, StumpfC, WickensM (2002) Analyzing mRNA-protein complexes using a yeast three-hybrid system. Methods 26: 123–141.

61. ClancyJL, NouschM, HumphreysDT, WestmanBJ, BeilharzTH, et al. (2007) Methods to analyze microRNA-mediated control of mRNA translation. Methods in enzymology 431: 83–111.

62. JedamzikB, EckmannCR (2009) Analysis of RNA-protein complexes by RNA coimmunoprecipitation and RT-PCR analysis from Caenorhabditis elegans. Cold Spring Harbor protocols 2009: pdb prot5300.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

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#