#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 3

The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in

English version České info

All cells require ribosomes, the cellular factories that produce proteins. A host of factors combine to produce the multiple complex units of a ribosome, many of which are still not well understood. Surprisingly, despite the ubiquitous requirement for ribosomes, defects in various ribosome biogenesis factors cause distinct and tissue specific phenotypes, collectively known as ribosomopathies. We examined the role of one ribosome biogenesis factor, Nol11, during embryonic development to determine if it too had a tissue specific phenotype. Here we show that expression of nol11 is strongly associated with the developing head in vertebrates and that insufficient Nol11 results in striking malformations of the craniofacial skeleton. We further show that reduced Nol11 impairs critical early steps in ribosome production, which triggers apoptosis within cell populations that contribute to the head. Increased cell death is at least partially the cause of the Nol11 craniofacial defect; reducing cell death rescues some of the craniofacial phenotype but not the ribosome biogenesis defect. In summary, we demonstrate for the first time that Nol11 is required for normal development of the vertebrate head and provide novel insight into the intriguing tissue proclivity of ribosomopathies.

Vyšlo v časopise: The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005018
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005018

Souhrn

All cells require ribosomes, the cellular factories that produce proteins. A host of factors combine to produce the multiple complex units of a ribosome, many of which are still not well understood. Surprisingly, despite the ubiquitous requirement for ribosomes, defects in various ribosome biogenesis factors cause distinct and tissue specific phenotypes, collectively known as ribosomopathies. We examined the role of one ribosome biogenesis factor, Nol11, during embryonic development to determine if it too had a tissue specific phenotype. Here we show that expression of nol11 is strongly associated with the developing head in vertebrates and that insufficient Nol11 results in striking malformations of the craniofacial skeleton. We further show that reduced Nol11 impairs critical early steps in ribosome production, which triggers apoptosis within cell populations that contribute to the head. Increased cell death is at least partially the cause of the Nol11 craniofacial defect; reducing cell death rescues some of the craniofacial phenotype but not the ribosome biogenesis defect. In summary, we demonstrate for the first time that Nol11 is required for normal development of the vertebrate head and provide novel insight into the intriguing tissue proclivity of ribosomopathies.

Zdroje

1. McCann KL, Baserga SJ (2013) Genetics. Mysterious ribosomopathies. Science 341 : 849–850. doi: 10.1126/science.1244156 23970686

2. Bolze A, Mahlaoui N, Byun M, Turner B, Trede N, et al. (2013) Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia. Science 340 : 976–978. doi: 10.1126/science.1234864 23579497

3. Butterfield RJ, Stevenson TJ, Xing L, Newcomb TM, Nelson B, et al. (2014) Congenital lethal motor neuron disease with a novel defect in ribosome biogenesis. Neurology.

4. Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, et al. (2002) A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis. Am J Hum Genet 71 : 1443–1449. 12417987

5. Dauwerse JG, Dixon J, Seland S, Ruivenkamp CA, van Haeringen A, et al. (2011) Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet 43 : 20–22. doi: 10.1038/ng.724 21131976

6. Dixon J, Jones NC, Sandell LL, Jayasinghe SM, Crane J, et al. (2006) Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities. Proc Natl Acad Sci U S A 103 : 13403–13408. 16938878

7. Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, et al. (1999) The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet 21 : 169–175. 9988267

8. Ebert BL, Pretz J, Bosco J, Chang CY, Tamayo P, et al. (2008) Identification of RPS14 as a 5q -⁠ syndrome gene by RNA interference screen. Nature 451 : 335–339. doi: 10.1038/nature06494 18202658

9. Freed EF, Baserga SJ (2010) The C-terminus of Utp4, mutated in childhood cirrhosis, is essential for ribosome biogenesis. Nucleic Acids Res 38 : 4798–4806. doi: 10.1093/nar/gkq185 20385600

10. Freed EF, Bleichert F, Dutca LM, Baserga SJ (2010) When ribosomes go bad: diseases of ribosome biogenesis. Mol Biosyst 6 : 481–493. doi: 10.1039/b919670f 20174677

11. Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, et al. (2008) Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet 83 : 769–780. doi: 10.1016/j.ajhg.2008.11.004 19061985

12. Hannan KM, Sanij E, Rothblum LI, Hannan RD, Pearson RB (2013) Dysregulation of RNA polymerase I transcription during disease. Biochim Biophys Acta 1829 : 342–360. doi: 10.1016/j.bbagrm.2012.10.014 23153826

13. Narla A, Ebert BL (2010) Ribosomopathies: human disorders of ribosome dysfunction. Blood 115 : 3196–3205. doi: 10.1182/blood-2009-10-178129 20194897

14. Teng T, Thomas G, Mercer CA (2013) Growth control and ribosomopathies. Curr Opin Genet Dev 23 : 63–71. doi: 10.1016/j.gde.2013.02.001 23490481

15. Trainor PA, Merrill AE (2014) Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders. Biochim Biophys Acta 1842 : 769–778. doi: 10.1016/j.bbadis.2013.11.010 24252615

16. Valdez BC, Henning D, So RB, Dixon J, Dixon MJ (2004) The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. Proc Natl Acad Sci U S A 101 : 10709–10714. 15249688

17. Trainor PA, Andrews BT (2013) Facial dysostoses: Etiology, pathogenesis and management. Am J Med Genet C Semin Med Genet 163 : 283–294.

18. Chai Y, Jiang X, Ito Y, Bringas P Jr., Han J, et al. (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127 : 1671–1679. 10725243

19. Dupin E, Creuzet S, Le Douarin NM (2006) The contribution of the neural crest to the vertebrate body. Adv Exp Med Biol 589 : 96–119. 17076277

20. Inman KE, Purcell P, Kume T, Trainor PA (2013) Interaction between Foxc1 and Fgf8 during mammalian jaw patterning and in the pathogenesis of syngnathia. PLoS Genet 9: e1003949. doi: 10.1371/journal.pgen.1003949 24385915

21. Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, et al. (2008) Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 14 : 125–133. doi: 10.1038/nm1725 18246078

22. Le Lievre CS, Le Douarin NM (1975) Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. J Embryol Exp Morphol 34 : 125–154. 1185098

23. Noden DM (1983) The role of the neural crest in patterning of avian cranial skeletal, connective, and muscle tissues. Dev Biol 96 : 144–165. 6825950

24. Olsson L, Falck P, Lopez K, Cobb J, Hanken J (2001) Cranial neural crest cells contribute to connective tissue in cranial muscles in the anuran amphibian, Bombina orientalis. Dev Biol 237 : 354–367. 11543620

25. Depew MJ, Lufkin T, Rubenstein JL (2002) Specification of jaw subdivisions by Dlx genes. Science 298 : 381–385. 12193642

26. Griffin JN, Compagnucci C, Hu D, Fish J, Klein O, et al. (2013) Fgf8 dosage determines midfacial integration and polarity within the nasal and optic capsules. Dev Biol 374 : 185–197. doi: 10.1016/j.ydbio.2012.11.014 23201021

27. Rijli FM, Mark M, Lakkaraju S, Dierich A, Dolle P, et al. (1993) A homeotic transformation is generated in the rostral branchial region of the head by disruption of Hoxa-2, which acts as a selector gene. Cell 75 : 1333–1349. 7903601

28. Trumpp A, Depew MJ, Rubenstein JL, Bishop JM, Martin GR (1999) Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev 13 : 3136–3148. 10601039

29. Basch ML, Bronner-Fraser M (2006) Neural crest inducing signals. Adv Exp Med Biol 589 : 24–31. 17076273

30. Pegoraro C, Monsoro-Burq AH (2013) Signaling and transcriptional regulation in neural crest specification and migration: lessons from xenopus embryos. Wiley Interdiscip Rev Dev Biol 2 : 247–259. doi: 10.1002/wdev.76 24009035

31. Aybar MJ, Nieto MA, Mayor R (2003) Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. Development 130 : 483–494. 12490555

32. Bhatt S, Diaz R, Trainor PA (2013) Signals and switches in Mammalian neural crest cell differentiation. Cold Spring Harb Perspect Biol 5.

33. Garcia-Castro M, Bronner-Fraser M (1999) Induction and differentiation of the neural crest. Curr Opin Cell Biol 11 : 695–698. 10600707

34. Garcia-Castro MI, Marcelle C, Bronner-Fraser M (2002) Ectodermal Wnt function as a neural crest inducer. Science 297 : 848–851. 12161657

35. Henras AK, Soudet J, Gerus M, Lebaron S, Caizergues-Ferrer M, et al. (2008) The post-transcriptional steps of eukaryotic ribosome biogenesis. Cell Mol Life Sci 65 : 2334–2359. doi: 10.1007/s00018-008-8027-0 18408888

36. Kressler D, Hurt E, Bassler J (2010) Driving ribosome assembly. Biochim Biophys Acta 1803 : 673–683. doi: 10.1016/j.bbamcr.2009.10.009 19879902

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

38. Woolford JL Jr., Baserga SJ (2013) Ribosome biogenesis in the yeast Saccharomyces cerevisiae. Genetics 195 : 643–681. doi: 10.1534/genetics.113.153197 24190922

39. Dragon F, Gallagher JE, Compagnone-Post PA, Mitchell BM, Porwancher KA, et al. (2002) A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis. Nature 417 : 967–970. 12068309

40. Prieto JL, McStay B (2007) Recruitment of factors linking transcription and processing of pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells. Genes Dev 21 : 2041–2054. 17699751

41. Sloan KE, Bohnsack MT, Schneider C, Watkins NJ (2014) The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA. RNA 20 : 540–550. doi: 10.1261/rna.043471.113 24550520

42. Gallagher JE, Dunbar DA, Granneman S, Mitchell BM, Osheim Y, et al. (2004) RNA polymerase I transcription and pre-rRNA processing are linked by specific SSU processome components. Genes Dev 18 : 2506–2517. 15489292

43. Zhao C, Andreeva V, Gibert Y, LaBonty M, Lattanzi V, et al. (2014) Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development. PLoS Genet 10: e1004074. doi: 10.1371/journal.pgen.1004074 24497835

44. Freed EF, Prieto JL, McCann KL, McStay B, Baserga SJ (2012) NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing. PLoS Genet 8: e1002892. doi: 10.1371/journal.pgen.1002892 22916032

45. Scherl A, Coute Y, Deon C, Calle A, Kindbeiter K, et al. (2002) Functional proteomic analysis of human nucleolus. Mol Biol Cell 13 : 4100–4109. 12429849

46. Wood HB, Episkopou V (1999) Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech Dev 86 : 197–201. 10446282

47. Rowitch DH, Kispert A, McMahon AP (1999) Pax-2 regulatory sequences that direct transgene expression in the developing neural plate and external granule cell layer of the cerebellum. Brain Res Dev Brain Res 117 : 99–108. 10536237

48. Hopwood ND, Pluck A, Gurdon JB (1989) MyoD expression in the forming somites is an early response to mesoderm induction in Xenopus embryos. EMBO J 8 : 3409–3417. 2555164

49. Carl TF, Dufton C, Hanken J, Klymkowsky MW (1999) Inhibition of neural crest migration in Xenopus using antisense slug RNA. Dev Biol 213 : 101–115. 10452849

50. Hong CS, Devotta A, Lee YH, Park BY, Saint-Jeannet JP (2014) Transcription factor AP2 epsilon (Tfap2e) regulates neural crest specification in Xenopus. Dev Neurobiol.

51. Soo K, O'Rourke MP, Khoo PL, Steiner KA, Wong N, et al. (2002) Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo. Dev Biol 247 : 251–270. 12086465

52. Blum M, Beyer T, Weber T, Vick P, Andre P, et al. (2009) Xenopus, an ideal model system to study vertebrate left-right asymmetry. Dev Dyn 238 : 1215–1225. doi: 10.1002/dvdy.21855 19208433

53. Chen CY, Croissant J, Majesky M, Topouzis S, McQuinn T, et al. (1996) Activation of the cardiac alpha-actin promoter depends upon serum response factor, Tinman homologue, Nkx-2.5, and intact serum response elements. Dev Genet 19 : 119–130. 8900044

54. Patterson KD, Drysdale TA, Krieg PA (2000) Embryonic origins of spleen asymmetry. Development 127 : 167–175. 10654610

55. Takebayashi-Suzuki K, Funami J, Tokumori D, Saito A, Watabe T, et al. (2003) Interplay between the tumor suppressor p53 and TGF beta signaling shapes embryonic body axes in Xenopus. Development 130 : 3929–3939. 12874116

56. Wallingford JB, Seufert DW, Virta VC, Vize PD (1997) p53 activity is essential for normal development in Xenopus. Curr Biol 7 : 747–757. 9368757

57. Yadav GV, Chakraborty A, Uechi T, Kenmochi N (2014) Ribosomal protein deficiency causes Tp53-independent erythropoiesis failure in zebrafish. Int J Biochem Cell Biol 49 : 1–7. doi: 10.1016/j.biocel.2014.01.006 24417973

58. Holmberg Olausson K, Nister M, Lindstrom MS (2012) p53-Dependent and-Independent Nucleolar Stress Responses. Cells 1 : 774–798. doi: 10.3390/cells1040774 24710530

59. Tafforeau L, Zorbas C, Langhendries JL, Mullineux ST, Stamatopoulou V, et al. (2013) The complexity of human ribosome biogenesis revealed by systematic nucleolar screening of Pre-rRNA processing factors. Mol Cell 51 : 539–551. doi: 10.1016/j.molcel.2013.08.011 23973377

60. Wang M, Anikin L, Pestov DG (2014) Two orthogonal cleavages separate subunit RNAs in mouse ribosome biogenesis. Nucleic Acids Res 42 : 11180–11191. doi: 10.1093/nar/gku787 25190460

61. Holzel M, Orban M, Hochstatter J, Rohrmoser M, Harasim T, et al. (2010) Defects in 18 S or 28 S rRNA processing activate the p53 pathway. J Biol Chem 285 : 6364–6370. doi: 10.1074/jbc.M109.054734 20056613

62. Zhang Y, Lu H (2009) Signaling to p53: ribosomal proteins find their way. Cancer Cell 16 : 369–377. doi: 10.1016/j.ccr.2009.09.024 19878869

63. Boulon S, Westman BJ, Hutten S, Boisvert FM, Lamond AI (2010) The nucleolus under stress. Mol Cell 40 : 216–227. doi: 10.1016/j.molcel.2010.09.024 20965417

64. Sondalle SB, Baserga SJ (2014) Human diseases of the SSU processome. Biochim Biophys Acta 1842 : 758–764. doi: 10.1016/j.bbadis.2013.11.004 24240090

65. Ellis SR (2014) Nucleolar stress in Diamond Blackfan anemia pathophysiology. Biochim Biophys Acta 1842 : 765–768. doi: 10.1016/j.bbadis.2013.12.013 24412987

66. Kondrashov N, Pusic A, Stumpf CR, Shimizu K, Hsieh AC, et al. (2011) Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145 : 383–397. doi: 10.1016/j.cell.2011.03.028 21529712

67. Boglev Y, Badrock AP, Trotter AJ, Du Q, Richardson EJ, et al. (2013) Autophagy induction is a Tor -⁠ and Tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis. PLoS Genet 9: e1003279. doi: 10.1371/journal.pgen.1003279 23408911

68. Khokha MK, Chung C, Bustamante EL, Gaw LW, Trott KA, et al. (2002) Techniques and probes for the study of Xenopus tropicalis development. Dev Dyn 225 : 499–510. 12454926

69. Hensey C, Gautier J (1998) Programmed cell death during Xenopus development: a spatio-temporal analysis. Dev Biol 203 : 36–48. 9806771

70. Pestov DG, Lapik YR, Lau LF (2008) Assays for ribosomal RNA processing and ribosome assembly. Curr Protoc Cell Biol Chapter 22: Unit 22 11.

71. Borovjagin AV, Gerbi SA (1999) U3 small nucleolar RNA is essential for cleavage at sites 1, 2 and 3 in pre-rRNA and determines which rRNA processing pathway is taken in Xenopus oocytes. J Mol Biol 286 : 1347–1363. 10064702

72. Borovjagin AV, Gerbi SA (2001) Xenopus U3 snoRNA GAC-Box A' and Box A sequences play distinct functional roles in rRNA processing. Mol Cell Biol 21 : 6210–6221. 11509664

73. Mougey EB, Pape LK, Sollner-Webb B (1993) A U3 small nuclear ribonucleoprotein-requiring processing event in the 5' external transcribed spacer of Xenopus precursor rRNA. Mol Cell Biol 13 : 5990–5998. 8413202

74. Peculis BA, Steitz JA (1993) Disruption of U8 nucleolar snRNA inhibits 5.8S and 28S rRNA processing in the Xenopus oocyte. Cell 73 : 1233–1245. 8513505

75. Savino R, Gerbi SA (1990) In vivo disruption of Xenopus U3 snRNA affects ribosomal RNA processing. EMBO J 9 : 2299–2308. 2357971

Štítky
Genetika Reprodukčná medicína
Článek NLRC5 Exclusively Transactivates MHC Class I and Related Genes through a Distinctive SXY Module
Článek Licensing of Primordial Germ Cells for Gametogenesis Depends on Genital Ridge Signaling
Článek A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes
Článek Genome-wide Association Study and Meta-Analysis Identify as Genome-wide Significant Susceptibility Gene for Bladder Exstrophy
Článek Mutations of Human , Encoding the Mitochondrial Asparaginyl-tRNA Synthetase, Cause Nonsyndromic Deafness and Leigh Syndrome
Článek Exome Sequencing in an Admixed Isolated Population Indicates Variants Confer a Risk for Specific Language Impairment
Článek Genome-Wide Association Studies in Dogs and Humans Identify as a Risk Variant for Cleft Lip and Palate
Článek Rapid Evolution of Recombinant for Xylose Fermentation through Formation of Extra-chromosomal Circular DNA
Článek Methyl Farnesoate Plays a Dual Role in Regulating Metamorphosis
Článek Maternal Co-ordinate Gene Regulation and Axis Polarity in the Scuttle Fly
Článek Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance
Článek Inhibition of Telomere Recombination by Inactivation of KEOPS Subunit Cgi121 Promotes Cell Longevity
Článek Clonality and Evolutionary History of Rhabdomyosarcoma
Článek HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice
Článek Methylation-Sensitive Expression of a DNA Demethylase Gene Serves As an Epigenetic Rheostat
Článek BREVIPEDICELLUS Interacts with the SWI2/SNF2 Chromatin Remodeling ATPase BRAHMA to Regulate and Expression in Control of Inflorescence Architecture
Článek Seizures Are Regulated by Ubiquitin-specific Peptidase 9 X-linked (USP9X), a De-Ubiquitinase
Článek The Fun30 Chromatin Remodeler Fft3 Controls Nuclear Organization and Chromatin Structure of Insulators and Subtelomeres in Fission Yeast
Článek A Cascade of Iron-Containing Proteins Governs the Genetic Iron Starvation Response to Promote Iron Uptake and Inhibit Iron Storage in Fission Yeast
Článek Mutation in MRPS34 Compromises Protein Synthesis and Causes Mitochondrial Dysfunction
Článek LRGUK-1 Is Required for Basal Body and Manchette Function during Spermatogenesis and Male Fertility
Článek Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in
Článek Effects on Murine Behavior and Lifespan of Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h Knockdown
Článek HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy
Článek A Conserved Domain in the Scc3 Subunit of Cohesin Mediates the Interaction with Both Mcd1 and the Cohesin Loader Complex
Článek Selective and Genetic Constraints on Pneumococcal Serotype Switching
Článek Bacterial Infection Drives the Expression Dynamics of microRNAs and Their isomiRs
Článek The GATA Factor Regulates . Developmental Timing by Promoting Expression of the Family MicroRNAs
Článek Accumulation of Glucosylceramide in the Absence of the Beta-Glucosidase GBA2 Alters Cytoskeletal Dynamics
Článek Reproductive Isolation of Hybrid Populations Driven by Genetic Incompatibilities
Článek The Contribution of Alu Elements to Mutagenic DNA Double-Strand Break Repair
Článek Systems Biology of Tissue-Specific Response to Reveals Differentiated Apoptosis in the Tick Vector
Článek Tfap2a Promotes Specification and Maturation of Neurons in the Inner Ear through Modulation of Bmp, Fgf and Notch Signaling
Článek The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors
Článek PHABULOSA Controls the Quiescent Center-Independent Root Meristem Activities in
Článek DNA Polymerase ζ-Dependent Lesion Bypass in Is Accompanied by Error-Prone Copying of Long Stretches of Adjacent DNA
Článek Examining the Evolution of the Regulatory Circuit Controlling Secondary Metabolism and Development in the Fungal Genus
Článek Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3
Článek GAGA Factor Maintains Nucleosome-Free Regions and Has a Role in RNA Polymerase II Recruitment to Promoters
Článek Neurospora Importin α Is Required for Normal Heterochromatic Formation and DNA Methylation
Článek Ccr4-Not Regulates RNA Polymerase I Transcription and Couples Nutrient Signaling to the Control of Ribosomal RNA Biogenesis
Článek Phenotype Specific Analyses Reveal Distinct Regulatory Mechanism for Chronically Activated p53
Článek A Systems-Level Interrogation Identifies Regulators of Blood Cell Number and Survival
Článek Morphological Mutations: Lessons from the Cockscomb
Článek Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast
Článek The Role of China in the Global Spread of the Current Cholera Pandemic
Článek The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes
Článek A Zinc Finger Motif-Containing Protein Is Essential for Chloroplast RNA Editing
Článek Resistance to Gray Leaf Spot of Maize: Genetic Architecture and Mechanisms Elucidated through Nested Association Mapping and Near-Isogenic Line Analysis
Článek Small Regulatory RNA-Induced Growth Rate Heterogeneity of
Článek Mitochondrial Dysfunction Reveals the Role of mRNA Poly(A) Tail Regulation in Oculopharyngeal Muscular Dystrophy Pathogenesis
Článek Complex Genomic Rearrangements at the Locus Include Triplication and Quadruplication
Článek Male-Biased Aganglionic Megacolon in the TashT Mouse Line Due to Perturbation of Silencer Elements in a Large Gene Desert of Chromosome 10
Článek Sex Ratio Meiotic Drive as a Plausible Evolutionary Mechanism for Hybrid Male Sterility
Článek Tertiary siRNAs Mediate Paramutation in .
Článek RECG Maintains Plastid and Mitochondrial Genome Stability by Suppressing Extensive Recombination between Short Dispersed Repeats
Článek Escape from X Inactivation Varies in Mouse Tissues
Článek Opposite Phenotypes of Muscle Strength and Locomotor Function in Mouse Models of Partial Trisomy and Monosomy 21 for the Proximal Region
Článek Glycosyl Phosphatidylinositol Anchor Biosynthesis Is Essential for Maintaining Epithelial Integrity during Embryogenesis
Článek Hyperdiverse Gene Cluster in Snail Host Conveys Resistance to Human Schistosome Parasites
Článek The Class Homeodomain Factors and Cooperate in . Embryonic Progenitor Cells to Regulate Robust Development
Článek Recombination between Homologous Chromosomes Induced by Unrepaired UV-Generated DNA Damage Requires Mus81p and Is Suppressed by Mms2p
Článek Synergistic Interactions between Orthologues of Genes Spanned by Human CNVs Support Multiple-Hit Models of Autism
Článek Gene Networks Underlying Convergent and Pleiotropic Phenotypes in a Large and Systematically-Phenotyped Cohort with Heterogeneous Developmental Disorders
Článek The ATM Signaling Cascade Promotes Recombination-Dependent Pachytene Arrest in Mouse Spermatocytes
Článek Combinatorial Control of Light Induced Chromatin Remodeling and Gene Activation in
Článek Linking Aβ42-Induced Hyperexcitability to Neurodegeneration, Learning and Motor Deficits, and a Shorter Lifespan in an Alzheimer’s Model
Článek The Complex Contributions of Genetics and Nutrition to Immunity in
Článek NatB Domain-Containing CRA-1 Antagonizes Hydrolase ACER-1 Linking Acetyl-CoA Metabolism to the Initiation of Recombination during . Meiosis
Článek Transcriptomic Profiling of Reveals Reprogramming of the Crp Regulon by Temperature and Uncovers Crp as a Master Regulator of Small RNAs
Článek Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption
Článek A Genomic Portrait of Haplotype Diversity and Signatures of Selection in Indigenous Southern African Populations
Článek Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin
Článek Inhibits Neuromuscular Junction Growth by Downregulating the BMP Receptor Thickveins
Článek Replicative DNA Polymerase δ but Not ε Proofreads Errors in and in
Článek Unsaturation of Very-Long-Chain Ceramides Protects Plant from Hypoxia-Induced Damages by Modulating Ethylene Signaling in
Článek The Small Protein MntS and Exporter MntP Optimize the Intracellular Concentration of Manganese
Článek A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension
Článek Pervasive Variation of Transcription Factor Orthologs Contributes to Regulatory Network Evolution
Článek Network Analyses Reveal Novel Aspects of ALS Pathogenesis
Článek A Role for the Budding Yeast Separase, Esp1, in Ty1 Element Retrotransposition
Článek Nab3 Facilitates the Function of the TRAMP Complex in RNA Processing via Recruitment of Rrp6 Independent of Nrd1
Článek A RecA Protein Surface Required for Activation of DNA Polymerase V
Článok vyšiel v časopise

PLOS Genetics

2015 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

nový kurz
Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, 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#