-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Intron Retention in the 5′UTR of the Novel ZIF2 Transporter Enhances Translation to Promote Zinc Tolerance in
Alternative splicing, which generates multiple messenger RNAs (mRNAs) from the same gene, is a key posttranscriptional regulatory mechanism in higher eukaryotes whose functional relevance in plants remains poorly understood. The sequestration of metal ions inside the vacuole of root cells is an important strategy employed by plants to cope with heavy metal toxicity. Here, we describe a new vacuolar membrane transporter of the model plant Arabidopsis thaliana, ZIF2, that confers tolerance to zinc (Zn) by promoting root immobilisation of the metal ion and thus its exclusion from the aerial parts of the plant. The ZIF2 gene is induced by exposure to excess Zn and undergoes alternative splicing, generating two mRNAs that differ solely in their non-coding regions and hence code for the same transporter. Interestingly, toxic Zn levels favour expression of the longer mRNA, which in turn confers higher plant tolerance to the metal. We show that the longer ZIF2 non-coding region markedly promotes translation of the downstream coding sequence into protein in a Zn-responsive fashion. Thus, our results indicate that by regulating translation efficiency of the ZIF2 mRNA, alternative splicing controls the amounts of the encoded membrane transporter and therefore plant Zn tolerance.
Vyšlo v časopise: Intron Retention in the 5′UTR of the Novel ZIF2 Transporter Enhances Translation to Promote Zinc Tolerance in. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004375
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004375Souhrn
Alternative splicing, which generates multiple messenger RNAs (mRNAs) from the same gene, is a key posttranscriptional regulatory mechanism in higher eukaryotes whose functional relevance in plants remains poorly understood. The sequestration of metal ions inside the vacuole of root cells is an important strategy employed by plants to cope with heavy metal toxicity. Here, we describe a new vacuolar membrane transporter of the model plant Arabidopsis thaliana, ZIF2, that confers tolerance to zinc (Zn) by promoting root immobilisation of the metal ion and thus its exclusion from the aerial parts of the plant. The ZIF2 gene is induced by exposure to excess Zn and undergoes alternative splicing, generating two mRNAs that differ solely in their non-coding regions and hence code for the same transporter. Interestingly, toxic Zn levels favour expression of the longer mRNA, which in turn confers higher plant tolerance to the metal. We show that the longer ZIF2 non-coding region markedly promotes translation of the downstream coding sequence into protein in a Zn-responsive fashion. Thus, our results indicate that by regulating translation efficiency of the ZIF2 mRNA, alternative splicing controls the amounts of the encoded membrane transporter and therefore plant Zn tolerance.
Zdroje
1. Marschner H (1995) Mineral Nutrition of Higher Plants. London: Academic Press.
2. ClemensS (2001) Molecular mechanisms of plant metal tolerance and homeostasis. Planta 212 : 475–486.
3. SinclairSA, KramerU (2012) The zinc homeostasis network of land plants. Biochim Biophys Acta 1823 : 1553–1567.
4. AssunçãoAG, SchatH, AartsMG (2010) Regulation of the adaptation to zinc deficiency in plants. Plant Signal Behav 5 : 1553–1555.
5. ErenE, ArguelloJM (2004) Arabidopsis HMA2, a divalent heavy metal-transporting P(IB)-type ATPase, is involved in cytoplasmic Zn2+ homeostasis. Plant Physiol 136 : 3712–3723.
6. TennstedtP, PeiskerD, BottcherC, TrampczynskaA, ClemensS (2009) Phytochelatin synthesis is essential for the detoxification of excess zinc and contributes significantly to the accumulation of zinc. Plant Physiol 149 : 938–948.
7. HaydonMJ, KawachiM, WirtzM, HillmerS, HellR, et al. (2012) Vacuolar nicotianamine has critical and distinct roles under iron deficiency and for zinc sequestration in Arabidopsis. Plant Cell 24 : 724–737.
8. KobaeY, UemuraT, SatoMH, OhnishiM, MimuraT, et al. (2004) Zinc transporter of Arabidopsis thaliana AtMTP1 is localized to vacuolar membranes and implicated in zinc homeostasis. Plant Cell Physiol 45 : 1749–1758.
9. Desbrosses-FonrougeAG, VoigtK, SchroderA, ArrivaultS, ThomineS, et al. (2005) Arabidopsis thaliana MTP1 is a Zn transporter in the vacuolar membrane which mediates Zn detoxification and drives leaf Zn accumulation. FEBS Lett 579 : 4165–4174.
10. ArrivaultS, SengerT, KramerU (2006) The Arabidopsis metal tolerance protein AtMTP3 maintains metal homeostasis by mediating Zn exclusion from the shoot under Fe deficiency and Zn oversupply. Plant J 46 : 861–879.
11. SongWY, ChoiKS, Kim doY, GeislerM, ParkJ, et al. (2010) Arabidopsis PCR2 is a zinc exporter involved in both zinc extrusion and long-distance zinc transport. Plant Cell 22 : 2237–2252.
12. WintzH, FoxT, WuYY, FengV, ChenW, et al. (2003) Expression profiles of Arabidopsis thaliana in mineral deficiencies reveal novel transporters involved in metal homeostasis. J Biol Chem 278 : 47644–47653.
13. MilnerMJ, SeamonJ, CraftE, KochianLV (2013) Transport properties of members of the ZIP family in plants and their role in Zn and Mn homeostasis. J Exp Bot 64 : 369–381.
14. ClausJ, Chavarria-KrauserA (2012) Modeling regulation of zinc uptake via ZIP transporters in yeast and plant roots. PLoS One 7: e37193.
15. VerretF, GravotA, AuroyP, LeonhardtN, DavidP, et al. (2004) Overexpression of AtHMA4 enhances root-to-shoot translocation of zinc and cadmium and plant metal tolerance. FEBS Lett 576 : 306–312.
16. MillsRF, FranciniA, Ferreira da RochaPS, BaccariniPJ, AylettM, et al. (2005) The plant P1B-type ATPase AtHMA4 transports Zn and Cd and plays a role in detoxification of transition metals supplied at elevated levels. FEBS Lett 579 : 783–791.
17. HussainD, HaydonMJ, WangY, WongE, ShersonSM, et al. (2004) P-type ATPase heavy metal transporters with roles in essential zinc homeostasis in Arabidopsis. Plant Cell 16 : 1327–1339.
18. KimYY, ChoiH, SegamiS, ChoHT, MartinoiaE, et al. (2009) AtHMA1 contributes to the detoxification of excess Zn(II) in Arabidopsis. Plant J 58 : 737–753.
19. MorelM, CrouzetJ, GravotA, AuroyP, LeonhardtN, et al. (2009) AtHMA3, a P1B-ATPase allowing Cd/Zn/Co/Pb vacuolar storage in Arabidopsis. Plant Physiol 149 : 894–904.
20. HaydonMJ, CobbettCS (2007) A novel major facilitator superfamily protein at the tonoplast influences zinc tolerance and accumulation in Arabidopsis. Plant Physiol 143 : 1705–1719.
21. LasatMM, BakerA, KochianLV (1996) Physiological Characterization of Root Zn2+ Absorption and Translocation to Shoots in Zn Hyperaccumulator and Nonaccumulator Species of Thlaspi. Plant Physiol 112 : 1715–1722.
22. TalkeIN, HanikenneM, KramerU (2006) Zinc-dependent global transcriptional control, transcriptional deregulation, and higher gene copy number for genes in metal homeostasis of the hyperaccumulator Arabidopsis halleri. Plant Physiol 142 : 148–167.
23. BecherM, TalkeIN, KrallL, KramerU (2004) Cross-species microarray transcript profiling reveals high constitutive expression of metal homeostasis genes in shoots of the zinc hyperaccumulator Arabidopsis halleri. Plant J 37 : 251–268.
24. WeberM, HaradaE, VessC, Roepenack-LahayeE, ClemensS (2004) Comparative microarray analysis of Arabidopsis thaliana and Arabidopsis halleri roots identifies nicotianamine synthase, a ZIP transporter and other genes as potential metal hyperaccumulation factors. Plant J 37 : 269–281.
25. PaoSS, PaulsenIT, SaierMHJr (1998) Major facilitator superfamily. Microbiol Mol Biol Rev 62 : 1–34.
26. ReaPA (2007) Plant ATP-binding cassette transporters. Annu Rev Plant Biol 58 : 347–375.
27. MarquezY, BrownJW, SimpsonC, BartaA, KalynaM (2012) Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis. Genome Res 22 : 1184–1195.
28. CarvalhoRF, FeijaoCV, DuqueP (2013) On the physiological significance of alternative splicing events in higher plants. Protoplasma 250 : 639–650.
29. RemyE, CabritoTR, BasterP, BatistaRA, TeixeiraMC, et al. (2013) A major facilitator superfamily transporter plays a dual role in polar auxin transport and drought stress tolerance in Arabidopsis. Plant Cell 25 : 901–926.
30. NelsonBK, CaiX, NebenfuhrA (2007) A multicolored set of in vivo organelle markers for co-localization studies in Arabidopsis and other plants. Plant J 51 : 1126–1136.
31. MacDiarmidCW, GaitherLA, EideD (2000) Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae. EMBO J 19 : 2845–2855.
32. ZhaoH, EideD (1996) The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae. J Biol Chem 271 : 23203–23210.
33. MiyashitaM, ShugyoM, NikawaJ (2003) Mutational analysis and localization of the inositol transporters of Saccharomyces cerevisiae. J Biosci Bioeng 96 : 291–297.
34. ShinH, ShinHS, DewbreGR, HarrisonMJ (2004) Phosphate transport in Arabidopsis: Pht1;1 and Pht1;4 play a major role in phosphate acquisition from both low - and high-phosphate environments. Plant J 39 : 629–642.
35. YooSD, ChoYH, SheenJ (2007) Arabidopsis mesophyll protoplasts: a versatile cell system for transient gene expression analysis. Nat Protoc 2 : 1565–1572.
36. Baena-GonzalezE, RollandF, TheveleinJM, SheenJ (2007) A central integrator of transcription networks in plant stress and energy signalling. Nature 448 : 938–942.
37. GrotzN, FoxT, ConnollyE, ParkW, GuerinotML, et al. (1998) Identification of a family of zinc transporter genes from Arabidopsis that respond to zinc deficiency. Proc Natl Acad Sci U S A 95 : 7220–7224.
38. ButtnerM (2007) The monosaccharide transporter(-like) gene family in Arabidopsis. FEBS Lett 581 : 2318–2324.
39. TsayYF, ChiuCC, TsaiCB, HoCH, HsuPK (2007) Nitrate transporters and peptide transporters. FEBS Lett 581 : 2290–2300.
40. NussaumeL, KannoS, JavotH, MarinE, PochonN, et al. (2011) Phosphate import in plants: focus on the PHT1 transporters. Front Plant Sci 2 : 83 doi: 10.3389/fpls.2011.00083
41. CarterC, PanS, ZouharJ, AvilaEL, GirkeT, et al. (2004) The vegetative vacuole proteome of Arabidopsis thaliana reveals predicted and unexpected proteins. Plant Cell 16 : 3285–3303.
42. JaquinodM, VilliersF, Kieffer-JaquinodS, HugouvieuxV, BruleyC, et al. (2007) A proteomics dissection of Arabidopsis thaliana vacuoles isolated from cell culture. Mol Cell Proteomics 6 : 394–412.
43. LanquarV, RamosMS, LelievreF, Barbier-BrygooH, Krieger-LiszkayA, et al. (2010) Export of vacuolar manganese by AtNRAMP3 and AtNRAMP4 is required for optimal photosynthesis and growth under manganese deficiency. Plant Physiol 152 : 1986–1999.
44. RichardO, PineauC, LoubetS, ChaliesC, VileD, et al. (2011) Diversity analysis of the response to Zn within the Arabidopsis thaliana species revealed a low contribution of Zn translocation to Zn tolerance and a new role for Zn in lateral root development. Plant Cell Environ 34 : 1065–1078.
45. KawachiM, KobaeY, MoriH, TomiokaR, LeeY, et al. (2009) A mutant strain Arabidopsis thaliana that lacks vacuolar membrane zinc transporter MTP1 revealed the latent tolerance to excessive zinc. Plant Cell Physiol 50 : 1156–1170.
46. LinYF, LiangHM, YangSY, BochA, ClemensS, et al. (2009) Arabidopsis IRT3 is a zinc-regulated and plasma membrane localized zinc/iron transporter. New Phytol 182 : 392–404.
47. WysockiR, TamasMJ (2010) How Saccharomyces cerevisiae copes with toxic metals and metalloids. FEMS Microbiol Rev 34 : 925–951.
48. MartinoiaE, MassonneauA, FrangneN (2000) Transport processes of solutes across the vacuolar membrane of higher plants. Plant Cell Physiol 41 : 1175–1186.
49. KrebsM, BeyhlD, GorlichE, Al-RasheidKA, MartenI, et al. (2010) Arabidopsis V-ATPase activity at the tonoplast is required for efficient nutrient storage but not for sodium accumulation. Proc Natl Acad Sci U S A 107 : 3251–3256.
50. ReddyAS, MarquezY, KalynaM, BartaA (2013) Complexity of the alternative splicing landscape in plants. Plant Cell 25 : 3657–3683.
51. StaigerD, BrownJW (2013) Alternative splicing at the intersection of biological timing, development, and stress responses. Plant Cell 25 : 3640–3656.
52. DujardinG, LafailleC, PetrilloE, BuggianoV, Gomez AcunaLI, et al. (2013) Transcriptional elongation and alternative splicing. Biochim Biophys Acta 1829 : 134–140.
53. ChunYS, ChoiE, YeoEJ, LeeJH, KimMS, et al. (2001) A new HIF-1 alpha variant induced by zinc ion suppresses HIF-1-mediated hypoxic responses. J Cell Sci 114 : 4051–4061.
54. HaraH, TakedaT, YamamotoN, FuruyaK, HiroseK, et al. (2013) Zinc-induced modulation of SRSF6 activity alters Bim splicing to promote generation of the most potent apoptotic isoform BimS. FEBS J 280 : 3313–3327.
55. MatsuuraH, TakenamiS, KuboY, UedaK, UedaA, et al. (2013) A computational and experimental approach reveals that the 5′-proximal region of the 5′-UTR has a Cis-regulatory signature responsible for heat stress-regulated mRNA translation in Arabidopsis. Plant Cell Physiol 54 : 474–483.
56. KawaguchiR, Bailey-SerresJ (2005) mRNA sequence features that contribute to translational regulation in Arabidopsis. Nucleic Acids Res 33 : 955–965.
57. AkuaT, ShaulO (2013) The Arabidopsis thaliana MHX gene includes an intronic element that boosts translation when localized in a 5′ UTR intron. J Exp Bot 64 : 4255–4270.
58. David-AssaelO, SaulH, SaulV, Mizrachy-DagriT, BerezinI, et al. (2005) Expression of AtMHX, an Arabidopsis vacuolar metal transporter, is repressed by the 5′ untranslated region of its gene. J Exp Bot 56 : 1039–1047.
59. SormaniR, DelannoyE, LageixS, BittonF, LanetE, et al. (2011) Sublethal cadmium intoxication in Arabidopsis thaliana impacts translation at multiple levels. Plant Cell Physiol 52 : 436–447.
60. DinkovaTD, ZepedaH, Martinez-SalasE, MartinezLM, Nieto-SoteloJ, et al. (2005) Cap-independent translation of maize Hsp101. Plant J 41 : 722–731.
61. MardanovaES, ZamchukLA, SkulachevMV, RavinNV (2008) The 5′ untranslated region of the maize alcohol dehydrogenase gene contains an internal ribosome entry site. Gene 420 : 11–16.
62. CloughSJ, BentAF (1998) Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. Plant J 16 : 735–743.
63. MurashigeT, SkoogF (1962) A revised medium for rapid growth and bioassays with tobacco tissue culture. Physiol Plant 15 : 473–497.
64. KarimiM, InzeD, DepickerA (2002) GATEWAY vectors for Agrobacterium-mediated plant transformation. Trends Plant Sci 7 : 193–195.
65. SundaresanV, SpringerP, VolpeT, HawardS, JonesJD, et al. (1995) Patterns of gene action in plant development revealed by enhancer trap and gene trap transposable elements. Genes Dev 9 : 1797–1810.
66. RemyE, CabritoTR, BatistaRA, TeixeiraMC, Sa-CorreiaI, et al. (2012) The Pht1;9 and Pht1;8 transporters mediate inorganic phosphate acquisition by the Arabidopsis thaliana root during phosphorus starvation. New Phytol 195 : 356–371.
67. SimonP (2003) Q-Gene: processing quantitative real-time RT-PCR data. Bioinformatics 19 : 1439–1440.
68. SilhavyD, MolnarA, LucioliA, SzittyaG, HornyikC, et al. (2002) A viral protein suppresses RNA silencing and binds silencing-generated, 21 - to 25-nucleotide double-stranded RNAs. EMBO J 21 : 3070–3080.
69. VoinnetO, RivasS, MestreP, BaulcombeD (2003) An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus. Plant J 33 : 949–956.
70. JansenG, WuC, SchadeB, ThomasDY, WhitewayM (2005) Drag&Drop cloning in yeast. Gene 344 : 43–51.
71. CabritoTR, TeixeiraMC, DuarteAA, DuqueP, Sá-CorreiaI (2009) Heterologous expression of a Tpo1 homolog from Arabidopsis thaliana confers resistance to the herbicide 2,4-D and other chemical stresses in yeast. Appl Microbiol Biotechnol 84 : 927–936.
72. FankhauserC, CasalJJ (2004) Phenotypic characterization of a photomorphogenic mutant. Plant J 39 : 747–760.
73. AbelS, TheologisA (1994) Transient transformation of Arabidopsis leaf protoplasts: a versatile experimental system to study gene expression. Plant J 5 : 421–427.
74. ConfrariaA, MartinhoC, EliasA, Rubio-SomozaI, Baena-GonzalezE (2013) miRNAs mediate SnRK1-dependent energy signaling in Arabidopsis. Front Plant Sci 4 : 197.
75. LaemmliUK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227 : 680–685.
76. Eaton AD, Clesceri LS, Rice EW, Greenberg AE, editors (2005) Standard Methods for the Examination of Water and Wastewater. 21st ed: American Public Health Association, American Water Works Association, Water Environment Federation.
77. LorenzR, BernhartSH, Honer Zu SiederdissenC, TaferH, FlammC, et al. (2011) ViennaRNA Package 2.0. Algorithms Mol Biol 6 : 26.
Štítky
Genetika Reprodukčná medicína
Článek Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin PathwayČlánek Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human DiseasesČlánek G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify LongevityČlánek PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial MatrixČlánek Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus ConflictsČlánek The Impact of Population Demography and Selection on the Genetic Architecture of Complex TraitsČlánek Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar AcidificationČlánek The Case for Junk DNA
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 5- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- Genetic Interactions Involving Five or More Genes Contribute to a Complex Trait in Yeast
- A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)
- Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling
- Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution
- Genome-Wide Nucleosome Positioning Is Orchestrated by Genomic Regions Associated with DNase I Hypersensitivity in Rice
- Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy
- Single Nucleotide Variants in Transcription Factors Associate More Tightly with Phenotype than with Gene Expression
- Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway
- Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases
- Epistatically Interacting Substitutions Are Enriched during Adaptive Protein Evolution
- Meiotic Drive Impacts Expression and Evolution of X-Linked Genes in Stalk-Eyed Flies
- G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity
- Population Genomic Analysis of Ancient and Modern Genomes Yields New Insights into the Genetic Ancestry of the Tyrolean Iceman and the Genetic Structure of Europe
- p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision
- Whole Exome Re-Sequencing Implicates and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction
- Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues
- R-loops Associated with Triplet Repeat Expansions Promote Gene Silencing in Friedreich Ataxia and Fragile X Syndrome
- PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix
- The Impairment of MAGMAS Function in Human Is Responsible for a Severe Skeletal Dysplasia
- Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Males
- Mlh2 Is an Accessory Factor for DNA Mismatch Repair in
- Activating Transcription Factor 6 Is Necessary and Sufficient for Alcoholic Fatty Liver Disease in Zebrafish
- The Spatiotemporal Program of DNA Replication Is Associated with Specific Combinations of Chromatin Marks in Human Cells
- Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts
- Genome-Wide Inference of Ancestral Recombination Graphs
- Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in
- SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates
- The Impact of Population Demography and Selection on the Genetic Architecture of Complex Traits
- Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation
- Genetic Dissection of the Female Head Transcriptome Reveals Widespread Allelic Heterogeneity
- Genome Sequencing and Comparative Genomics of the Broad Host-Range Pathogen AG8
- Copy Number Variation Is a Fundamental Aspect of the Placental Genome
- GOLPH3 Is Essential for Contractile Ring Formation and Rab11 Localization to the Cleavage Site during Cytokinesis in
- Hox Transcription Factors Access the RNA Polymerase II Machinery through Direct Homeodomain Binding to a Conserved Motif of Mediator Subunit Med19
- Drosha Promotes Splicing of a Pre-microRNA-like Alternative Exon
- Predicting the Minimal Translation Apparatus: Lessons from the Reductive Evolution of
- PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF
- Enhanced Interaction between Pseudokinase and Kinase Domains in Gcn2 stimulates eIF2α Phosphorylation in Starved Cells
- A HECT Ubiquitin-Protein Ligase as a Novel Candidate Gene for Altered Quinine and Quinidine Responses in
- dGTP Starvation in Provides New Insights into the Thymineless-Death Phenomenon
- Phosphorylation Modulates Clearance of Alpha-Synuclein Inclusions in a Yeast Model of Parkinson's Disease
- RPM-1 Uses Both Ubiquitin Ligase and Phosphatase-Based Mechanisms to Regulate DLK-1 during Neuronal Development
- More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta
- More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta
- Heritable Transmission of Stress Resistance by High Dietary Glucose in
- Revertant Mutation Releases Confined Lethal Mutation, Opening Pandora's Box: A Novel Genetic Pathogenesis
- Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification
- A Genome-Wide Assessment of the Role of Untagged Copy Number Variants in Type 1 Diabetes
- Selectivity in Genetic Association with Sub-classified Migraine in Women
- A Lack of Parasitic Reduction in the Obligate Parasitic Green Alga
- The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast
- Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma
- Six Homeoproteins and a linc-RNA at the Fast MYH Locus Lock Fast Myofiber Terminal Phenotype
- EDR1 Physically Interacts with MKK4/MKK5 and Negatively Regulates a MAP Kinase Cascade to Modulate Plant Innate Immunity
- Genes That Bias Mendelian Segregation
- The Case for Junk DNA
- An In Vivo EGF Receptor Localization Screen in Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
- Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder
- Hyperactivated Wnt Signaling Induces Synthetic Lethal Interaction with Rb Inactivation by Elevating TORC1 Activities
- Mutations in the Cholesterol Transporter Gene Are Associated with Excessive Hair Overgrowth
- Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland
- A Novel CH Transcription Factor that Regulates Expression Interdependently with GliZ in
- Phosphorylation of a WRKY Transcription Factor by MAPKs Is Required for Pollen Development and Function in
- Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics
- Spermatid Cyst Polarization in Depends upon and the CPEB Family Translational Regulator
- Insights into the Genetic Structure and Diversity of 38 South Asian Indians from Deep Whole-Genome Sequencing
- Intron Retention in the 5′UTR of the Novel ZIF2 Transporter Enhances Translation to Promote Zinc Tolerance in
- A Dominant-Negative Mutation of Mouse Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation
- Biased, Non-equivalent Gene-Proximal and -Distal Binding Motifs of Orphan Nuclear Receptor TR4 in Primary Human Erythroid Cells
- Ras-Mediated Deregulation of the Circadian Clock in Cancer
- Retinoic Acid-Related Orphan Receptor γ (RORγ): A Novel Participant in the Diurnal Regulation of Hepatic Gluconeogenesis and Insulin Sensitivity
- Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions
- Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2
- Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression
- Allele-Specific Genome-wide Profiling in Human Primary Erythroblasts Reveal Replication Program Organization
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix
- Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy
- Phosphorylation of a WRKY Transcription Factor by MAPKs Is Required for Pollen Development and Function in
- p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy