-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly
Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small (SSU) and large subunit (LSU). We demonstrate here that the m5C methyltransferase NSUN4, which forms a complex with MTERF4, is essential in mitochondrial ribosomal biogenesis as mitochondrial translation is abolished in conditional Nsun4 mouse knockouts. Deep sequencing of bisulfite-treated RNA shows that NSUN4 methylates cytosine 911 in 12S rRNA (m5C911) of the SSU. Surprisingly, NSUN4 does not need MTERF4 to generate this modification. Instead, the NSUN4/MTERF4 complex is required to assemble the SSU and LSU to form a monosome. NSUN4 is thus a dual function protein, which on the one hand is needed for 12S rRNA methylation and, on the other hand interacts with MTERF4 to facilitate monosome assembly. The presented data suggest that NSUN4 has a key role in controlling a final step in ribosome biogenesis to ensure that only the mature SSU and LSU are assembled.
Vyšlo v časopise: NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly. PLoS Genet 10(2): e32767. doi:10.1371/journal.pgen.1004110
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004110Souhrn
Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small (SSU) and large subunit (LSU). We demonstrate here that the m5C methyltransferase NSUN4, which forms a complex with MTERF4, is essential in mitochondrial ribosomal biogenesis as mitochondrial translation is abolished in conditional Nsun4 mouse knockouts. Deep sequencing of bisulfite-treated RNA shows that NSUN4 methylates cytosine 911 in 12S rRNA (m5C911) of the SSU. Surprisingly, NSUN4 does not need MTERF4 to generate this modification. Instead, the NSUN4/MTERF4 complex is required to assemble the SSU and LSU to form a monosome. NSUN4 is thus a dual function protein, which on the one hand is needed for 12S rRNA methylation and, on the other hand interacts with MTERF4 to facilitate monosome assembly. The presented data suggest that NSUN4 has a key role in controlling a final step in ribosome biogenesis to ensure that only the mature SSU and LSU are assembled.
Zdroje
1. Cavdar KocE, BurkhartW, BlackburnK, MoseleyA, SpremulliLL (2001) The small subunit of the mammalian mitochondrial ribosome. Identification of the full complement of ribosomal proteins present. J Biol Chem 276 : 19363–19374.
2. KocEC, BurkhartW, BlackburnK, MoyerMB, SchlatzerDM, et al. (2001) The large subunit of the mammalian mitochondrial ribosome. Analysis of the complement of ribosomal proteins present. J Biol Chem 276 : 43958–43969.
3. SiibakT, RemmeJ (2010) Subribosomal particle analysis reveals the stages of bacterial ribosome assembly at which rRNA nucleotides are modified. RNA 16 : 2023–2032.
4. MetodievMD, LeskoN, ParkCB, CamaraY, ShiY, et al. (2009) Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab 9 : 386–397.
5. LeeKW, Okot-KotberC, LacombJF, BogenhagenDF (2013) Mitochondrial rRNA Methyltransferase Family Members are Positioned to Modify Nascent rRNA in Foci Near the mtDNA Nucleoid. J Biol Chem 288(43): 31386–99.
6. BaerRJ, DubinDT (1981) Methylated regions of hamster mitochondrial ribosomal RNA: structural and functional correlates. Nucleic Acids Res 9 : 323–337.
7. DecaturWA, FournierMJ (2002) rRNA modifications and ribosome function. Trends Biochem Sci 27 : 344–351.
8. CamaraY, Asin-CayuelaJ, ParkCB, MetodievMD, ShiY, et al. (2011) MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome. Cell Metab 13 : 527–539.
9. SpahrH, HabermannB, GustafssonCM, LarssonNG, HallbergBM (2012) Structure of the human MTERF4-NSUN4 protein complex that regulates mitochondrial ribosome biogenesis. Proc Natl Acad Sci U S A 109 : 15253–15258.
10. YakubovskayaE, GujaKE, MejiaE, CastanoS, HambardjievaE, et al. (2012) Structure of the essential MTERF4:NSUN4 protein complex reveals how an MTERF protein collaborates to facilitate rRNA modification. Structure 20 : 1940–1947.
11. GuXR, GustafssonC, KuJ, YuM, SantiDV (1999) Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli. Biochemistry 38 : 4053–4057.
12. AndersenNM, DouthwaiteS (2006) YebU is a m5C methyltransferase specific for 16 S rRNA nucleotide 1407. J Mol Biol 359 : 777–786.
13. PurtaE, O'ConnorM, BujnickiJM, DouthwaiteS (2008) YccW is the m5C methyltransferase specific for 23S rRNA nucleotide 1962. J Mol Biol 383 : 641–651.
14. DemirciH, LarsenLH, HansenT, RasmussenA, CadambiA, et al. (2010) Multi-site-specific 16S rRNA methyltransferase RsmF from Thermus thermophilus. RNA 16 : 1584–1596.
15. WredenbergA, LagougeM, BraticA, MetodievMD, SpahrH, et al. (2013) MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals. PLoS Genet 9: e1003178.
16. DagaA, MicolV, HessD, AebersoldR, AttardiG (1993) Molecular characterization of the transcription termination factor from human mitochondria. J Biol Chem 268 : 8123–8130.
17. KruseB, NarasimhanN, AttardiG (1989) Termination of transcription in human mitochondria: identification and purification of a DNA binding protein factor that promotes termination. Cell 58 : 391–397.
18. MartinM, ChoJ, CesareAJ, GriffithJD, AttardiG (2005) Termination factor-mediated DNA loop between termination and initiation sites drives mitochondrial rRNA synthesis. Cell 123 : 1227–1240.
19. TerziogluM, RuzzenenteB, HarmelJ, MourierA, JemtE, et al. (2013) MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation. Cell Metab 17 : 618–626.
20. WenzT, LucaC, TorracoA, MoraesCT (2009) mTERF2 regulates oxidative phosphorylation by modulating mtDNA transcription. Cell Metab 9 : 499–511.
21. ParkCB, Asin-CayuelaJ, CamaraY, ShiY, PellegriniM, et al. (2007) MTERF3 is a negative regulator of mammalian mtDNA transcription. Cell 130 : 273–285.
22. RuzzenenteB, MetodievMD, WredenbergA, BraticA, ParkCB, et al. (2011) LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. EMBO J 31 : 443–456.
23. SchaeferM, PollexT, HannaK, LykoF (2009) RNA cytosine methylation analysis by bisulfite sequencing. Nucleic Acids Res 37: e12.
24. KingMY, RedmanKL (2002) RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine. Biochemistry 41 : 11218–11225.
25. RedmanKL (2006) Assembly of protein-RNA complexes using natural RNA and mutant forms of an RNA cytosine methyltransferase. Biomacromolecules 7 : 3321–3326.
26. SeibelP, Di NunnoC, KukatC, SchaferI, Del BoR, et al. (2008) Cosegregation of novel mitochondrial 16S rRNA gene mutations with the age-associated T414G variant in human cybrids. Nucleic Acids Res 36 : 5872–5881.
27. LafontaineD, VandenhauteJ, TollerveyD (1995) The 18S rRNA dimethylase Dim1p is required for pre-ribosomal RNA processing in yeast. Genes Dev 9 : 2470–2481.
28. LafontaineDL, PreissT, TollerveyD (1998) Yeast 18S rRNA dimethylase Dim1p: a quality control mechanism in ribosome synthesis? Mol Cell Biol 18 : 2360–2370.
29. ThammanaP, HeldWA (1974) Methylation of 16S RNA during ribosome assembly in vitro. Nature 251 : 682–686.
30. XuZ, O'FarrellHC, RifeJP, CulverGM (2008) A conserved rRNA methyltransferase regulates ribosome biogenesis. Nat Struct Mol Biol 15 : 534–536.
31. DemirciH, GregoryST, DahlbergAE, JoglG (2008) Crystal structure of the Thermus thermophilus 16 S rRNA methyltransferase RsmC in complex with cofactor and substrate guanosine. J Biol Chem 283 : 26548–26556.
32. ConnollyK, CulverG (2009) Deconstructing ribosome construction. Trends Biochem Sci 34 : 256–263.
33. ChenY, Sierzputowska-GraczH, GuentherR, EverettK, AgrisPF (1993) 5-Methylcytidine is required for cooperative binding of Mg2+ and a conformational transition at the anticodon stem-loop of yeast phenylalanine tRNA. Biochemistry 32 : 10249–10253.
34. AlexandrovA, ChernyakovI, GuW, HileySL, HughesTR, et al. (2006) Rapid tRNA decay can result from lack of nonessential modifications. Mol Cell 21 : 87–96.
35. MotorinY, HelmM (2011) RNA nucleotide methylation. Wiley Interdiscip Rev RNA 2 : 611–631.
36. KruegerF, AndrewsSR (2011) Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27 : 1571–1572.
37. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.
38. EnriquezJA, Perez-MartosA, Lopez-PerezMJ, MontoyaJ (1996) In organello RNA synthesis system from mammalian liver and brain. Methods Enzymol 264 : 50–57.
39. Fernandez-VizarraE, FerrinG, Perez-MartosA, Fernandez-SilvaP, ZevianiM, et al. (2010) Isolation of mitochondria for biogenetical studies: An update. Mitochondrion 10 : 253–262.
40. CoteC, PoirierJ, BouletD (1989) Expression of the mammalian mitochondrial genome. Stability of mitochondrial translation products as a function of membrane potential. J Biol Chem 264 : 8487–8490.
41. SieversF, WilmA, DineenD, GibsonTJ, KarplusK, et al. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7 : 539.
42. NicholasKB, H.BN, Deerfield IIDW (1997) GeneDoc: Analysis and Visualization of Genetic Variation. embnetnews 4 : 4.
43. LarssonNG, WangJ, WilhelmssonH, OldforsA, RustinP, et al. (1998) Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 18 : 231–236.
44. UleJ, JensenK, MeleA, DarnellRB (2005) CLIP: a method for identifying protein-RNA interaction sites in living cells. Methods 37 : 376–386.
45. HafnerM, LandthalerM, BurgerL, KhorshidM, HausserJ, et al. (2010) PAR-CliP–a method to identify transcriptome-wide the binding sites of RNA binding proteins. J Vis Exp (41): pii: 2034.
Štítky
Genetika Reprodukčná medicína
Článek Natural Polymorphisms in Influence Negative Selection and CD4∶CD8 Lineage Commitment in the RatČlánek MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease PathogenesisČlánek Comparative RNAi Screens in and Reveal the Impact of Developmental System Drift on Gene FunctionČlánek Mutation of SLC35D3 Causes Metabolic Syndrome by Impairing Dopamine Signaling in Striatal D1 Neurons
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 2- 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
- Fifteen Years Later: Hard and Soft Selection Sweeps Confirm a Large Population Number for HIV In Vivo
- The Same but Different: Worms Reveal the Pervasiveness of Developmental System Drift
- Serine Carboxypeptidase SCPEP1 and Cathepsin A Play Complementary Roles in Regulation of Vasoconstriction via Inactivation of Endothelin-1
- Coherent Functional Modules Improve Transcription Factor Target Identification, Cooperativity Prediction, and Disease Association
- A Long-Chain Flavodoxin Protects from Oxidative Stress and Host Bacterial Clearance
- Mammalian E-type Cyclins Control Chromosome Pairing, Telomere Stability and CDK2 Localization in Male Meiosis
- Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective
- Transcriptome-Wide Analyses of 5′-Ends in RNase J Mutants of a Gram-Positive Pathogen Reveal a Role in RNA Maturation, Regulation and Degradation
- Selective Disruption of Aurora C Kinase Reveals Distinct Functions from Aurora B Kinase during Meiosis in Mouse Oocytes
- X Chromosome Control of Meiotic Chromosome Synapsis in Mouse Inter-Subspecific Hybrids
- A Cohesin-Independent Role for NIPBL at Promoters Provides Insights in CdLS
- Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa
- Classic Selective Sweeps Revealed by Massive Sequencing in Cattle
- Genomic Networks of Hybrid Sterility
- Natural Polymorphisms in Influence Negative Selection and CD4∶CD8 Lineage Commitment in the Rat
- Oxidative Stress Is Not a Major Contributor to Somatic Mitochondrial DNA Mutations
- Molecular Identification of Collagen 17a1 as a Major Genetic Modifier of Laminin Gamma 2 Mutation-Induced Junctional Epidermolysis Bullosa in Mice
- Uncoupling of Molecular Maturation from Peripheral Target Innervation in Nociceptors Expressing a Chimeric TrkA/TrkC Receptor
- MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis
- Loss of Trabid, a New Negative Regulator of the Immune-Deficiency Pathway at the Level of TAK1, Reduces Life Span
- Targeted Ablation of Nesprin 1 and Nesprin 2 from Murine Myocardium Results in Cardiomyopathy, Altered Nuclear Morphology and Inhibition of the Biomechanical Gene Response
- Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease
- CEP-1, the p53 Homolog, Mediates Opposing Longevity Outcomes in Mitochondrial Electron Transport Chain Mutants
- Transcriptomics and Functional Genomics of ROS-Induced Cell Death Regulation by
- Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in
- Cascades of Genetic Instability Resulting from Compromised Break-Induced Replication
- Serine- and Threonine/Valine-Dependent Activation of PDK and Tor Orthologs Converge on Sch9 to Promote Aging
- Zfp322a Regulates Mouse ES Cell Pluripotency and Enhances Reprogramming Efficiency
- Insertional Mutagenesis and Deep Profiling Reveals Gene Hierarchies and a -Dependent Bottleneck in Lymphomagenesis
- DAAM Is Required for Thin Filament Formation and Sarcomerogenesis during Muscle Development in Drosophila
- Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis
- High-Resolution Profiling of Stationary-Phase Survival Reveals Yeast Longevity Factors and Their Genetic Interactions
- Comparative RNAi Screens in and Reveal the Impact of Developmental System Drift on Gene Function
- Accurate and Robust Genomic Prediction of Celiac Disease Using Statistical Learning
- Sex-Specific Embryonic Gene Expression in Species with Newly Evolved Sex Chromosomes
- Chromosome X-Wide Association Study Identifies Loci for Fasting Insulin and Height and Evidence for Incomplete Dosage Compensation
- Negative Feedback and Transcriptional Overshooting in a Regulatory Network for Horizontal Gene Transfer
- DNA Sequence Explains Seemingly Disordered Methylation Levels in Partially Methylated Domains of Mammalian Genomes
- Insights into the Genomic Landscape: Comparative Genomics Reveals Variations in Ploidy and Nutrient Utilisation Potential amongst Wine Isolates
- Molecular Evidence for the Inverse Comorbidity between Central Nervous System Disorders and Cancers Detected by Transcriptomic Meta-analyses
- The Centriolar Satellite Protein AZI1 Interacts with BBS4 and Regulates Ciliary Trafficking of the BBSome
- Fine-Mapping the Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer
- Transmission Distortion Affecting Human Noncrossover but Not Crossover Recombination: A Hidden Source of Meiotic Drive
- A Variant in the Neuropeptide Receptor is a Major Determinant of Growth and Physiology
- Mutation of SLC35D3 Causes Metabolic Syndrome by Impairing Dopamine Signaling in Striatal D1 Neurons
- NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly
- MicroRNA-133 Inhibits Behavioral Aggregation by Controlling Dopamine Synthesis in Locusts
- Convergence of Light and ABA Signaling on the Promoter
- Arf4 Is Required for Mammalian Development but Dispensable for Ciliary Assembly
- Distinct Requirements for Cranial Ectoderm and Mesenchyme-Derived Wnts in Specification and Differentiation of Osteoblast and Dermal Progenitors
- Chk2 and P53 Regulate the Transmission of Healed Chromosomes in the Male Germline
- Ddc2 Mediates Mec1 Activation through a Ddc1- or Dpb11-Independent Mechanism
- Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations
- Euchromatic Transposon Insertions Trigger Production of Novel Pi- and Endo-siRNAs at the Target Sites in the Germline
- miR-100 Induces Epithelial-Mesenchymal Transition but Suppresses Tumorigenesis, Migration and Invasion
- Canine Hereditary Ataxia in Old English Sheepdogs and Gordon Setters Is Associated with a Defect in the Autophagy Gene Encoding
- Within-Host Spatiotemporal Dynamics of Plant Virus Infection at the Cellular Level
- Analysis of Meiosis in SUN1 Deficient Mice Reveals a Distinct Role of SUN2 in Mammalian Meiotic LINC Complex Formation and Function
- Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links
- Mechanistically Distinct Mouse Models for -Associated Retinopathy
- DAF-16/FoxO Directly Regulates an Atypical AMP-Activated Protein Kinase Gamma Isoform to Mediate the Effects of Insulin/IGF-1 Signaling on Aging in
- Chromosome I Controls Chromosome II Replication in
- Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma
- The Iodotyrosine Deiodinase Ortholog SUP-18 Functions through a Conserved Channel SC-Box to Regulate the Muscle Two-Pore Domain Potassium Channel SUP-9
- The Genome of Highlights a Fish Pathogen Adapted to Fluctuating Environments
- Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in and
- The Streamlined Genome of spp. Relative to Human Pathogenic Kinetoplastids Reveals a Parasite Tailored for Plants
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links
- A Cohesin-Independent Role for NIPBL at Promoters Provides Insights in CdLS
- Classic Selective Sweeps Revealed by Massive Sequencing in Cattle
- Arf4 Is Required for Mammalian Development but Dispensable for Ciliary Assembly
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