MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals
Regulation of mitochondrial DNA (mtDNA) expression is critical for the control of oxidative phosphorylation in response to physiological demand, and this regulation is often impaired in disease and aging. We have previously shown that mitochondrial transcription termination factor 3 (MTERF3) is a key regulator that represses mtDNA transcription in the mouse, but its molecular mode of action has remained elusive. Based on the hypothesis that key regulatory mechanisms for mtDNA expression are conserved in metazoans, we analyzed Mterf3 knockout and knockdown flies. We demonstrate here that decreased expression of MTERF3 not only leads to activation of mtDNA transcription, but also impairs assembly of the large mitochondrial ribosomal subunit. This novel function of MTERF3 in mitochondrial ribosomal biogenesis is conserved in the mouse, thus we identify a novel and unexpected role for MTERF3 in coordinating the crosstalk between transcription and translation for the regulation of mammalian mtDNA gene expression.
Vyšlo v časopise:
MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals. PLoS Genet 9(1): e32767. doi:10.1371/journal.pgen.1003178
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003178
Souhrn
Regulation of mitochondrial DNA (mtDNA) expression is critical for the control of oxidative phosphorylation in response to physiological demand, and this regulation is often impaired in disease and aging. We have previously shown that mitochondrial transcription termination factor 3 (MTERF3) is a key regulator that represses mtDNA transcription in the mouse, but its molecular mode of action has remained elusive. Based on the hypothesis that key regulatory mechanisms for mtDNA expression are conserved in metazoans, we analyzed Mterf3 knockout and knockdown flies. We demonstrate here that decreased expression of MTERF3 not only leads to activation of mtDNA transcription, but also impairs assembly of the large mitochondrial ribosomal subunit. This novel function of MTERF3 in mitochondrial ribosomal biogenesis is conserved in the mouse, thus we identify a novel and unexpected role for MTERF3 in coordinating the crosstalk between transcription and translation for the regulation of mammalian mtDNA gene expression.
Zdroje
1. TaylorRW, TurnbullDM (2005) Mitochondrial DNA mutations in human disease. Nat Rev Genet 6: 389–402.
2. GreavesLC, TurnbullDM (2009) Mitochondrial DNA mutations and ageing. Biochim Biophys Acta 1790: 1015–1020.
3. LarssonNG (2010) Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem 79: 683–706.
4. FalkenbergM, LarssonNG, GustafssonCM (2007) DNA replication and transcription in mammalian mitochondria. Annu Rev Biochem 76: 679–699.
5. ParkCB, Asin-CayuelaJ, CamaraY, ShiY, PellegriniM, et al. (2007) MTERF3 is a negative regulator of mammalian mtDNA transcription. Cell 130: 273–285.
6. FalkenbergM, GaspariM, RantanenA, TrifunovicA, LarssonNG, et al. (2002) Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet 31: 289–294.
7. NgoHB, KaiserJT, ChanDC (2011) The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. Nat Struct Mol Biol 18: 1290–1296.
8. Rubio-CosialsA, SidowJF, Jimenez-MenendezN, Fernandez-MillanP, MontoyaJ, et al. (2011) Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nat Struct Mol Biol 18: 1281–1289.
9. ShiY, DierckxA, WanrooijPH, WanrooijS, LarssonNG, et al. (2012) Mammalian transcription factor A is a core component of the mitochondrial transcription machinery. Proc Natl Acad Sci U S A 109: 16510–16515.
10. EkstrandMI, FalkenbergM, RantanenA, ParkCB, GaspariM, et al. (2004) Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 13: 935–944.
11. HallbergBM, LarssonNG (2011) TFAM forces mtDNA to make a U-turn. Nat Struct Mol Biol 18: 1179–1181.
12. KukatC, WurmCA, SpahrH, FalkenbergM, LarssonNG, et al. (2011) Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proc Natl Acad Sci U S A 108: 13534–13539.
13. 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.
14. LitoninD, SologubM, ShiY, SavkinaM, AnikinM, et al. (2010) Human mitochondrial transcription revisited: only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro. J Biol Chem 285: 18129–18133.
15. RingelR, SologubM, MorozovYI, LitoninD, CramerP, et al. (2011) Structure of human mitochondrial RNA polymerase. Nature 478: 269–273.
16. SologubM, LitoninD, AnikinM, MustaevA, TemiakovD (2009) TFB2 is a transient component of the catalytic site of the human mitochondrial RNA polymerase. Cell 139: 934–944.
17. ShuttTE, ShadelGS (2010) A compendium of human mitochondrial gene expression machinery with links to disease. Environ Mol Mutagen 51: 360–379.
18. SondheimerN, FangJK, PolyakE, FalkMJ, AvadhaniNG (2010) Leucine-rich pentatricopeptide-repeat containing protein regulates mitochondrial transcription. Biochemistry 49: 7467–7473.
19. 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.
20. BraticA, WredenbergA, GronkeS, StewartJB, MourierA, et al. (2011) The bicoid stability factor controls polyadenylation and expression of specific mitochondrial mRNAs in Drosophila melanogaster. PLoS Genet 7: e1002324 doi:10.1371/journal.pgen.1002324.
21. KempJP, SmithPM, PyleA, NeeveVC, TuppenHA, et al. (2011) Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency. Brain 134: 183–195.
22. RorbachJ, Soleimanpour-LichaeiR, LightowlersRN, Chrzanowska-LightowlersZM (2007) How do mammalian mitochondria synthesize proteins? Biochem Soc Trans 35: 1290–1291.
23. 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.
24. LinderT, ParkCB, Asin-CayuelaJ, PellegriniM, LarssonNG, et al. (2005) A family of putative transcription termination factors shared amongst metazoans and plants. Curr Genet 48: 265–269.
25. Asin-CayuelaJ, SchwendT, FargeG, GustafssonCM (2005) The human mitochondrial transcription termination factor (mTERF) is fully active in vitro in the non-phosphorylated form. J Biol Chem 280: 25499–25505.
26. Fernandez-SilvaP, Martinez-AzorinF, MicolV, AttardiG (1997) The human mitochondrial transcription termination factor (mTERF) is a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions. EMBO J 16: 1066–1079.
27. GustafssonCM, LarssonNG (2010) MTERF1 gives mtDNA an unusual twist. Cell Metab 12: 3–4.
28. Jimenez-MenendezN, Fernandez-MillanP, Rubio-CosialsA, ArnanC, MontoyaJ, et al. (2010) Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat. Nat Struct Mol Biol 17: 891–893.
29. YakubovskayaE, MejiaE, ByrnesJ, HambardjievaE, Garcia-DiazM (2010) Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription. Cell 141: 982–993.
30. MartinM, ChoJ, CesareAJ, GriffithJD, AttardiG (2005) Termination factor-mediated DNA loop between termination and initiation sites drives mitochondrial rRNA synthesis. Cell 123: 1227–1240.
31. WenzT, LucaC, TorracoA, MoraesCT (2009) mTERF2 regulates oxidative phosphorylation by modulating mtDNA transcription. Cell Metab 9: 499–511.
32. PellegriniM, Asin-CayuelaJ, Erdjument-BromageH, TempstP, LarssonNG, et al. (2009) MTERF2 is a nucleoid component in mammalian mitochondria. Biochim Biophys Acta 1787: 296–302.
33. 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.
34. 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.
35. MercerTR, NephS, DingerME, CrawfordJ, SmithMA, et al. (2011) The human mitochondrial transcriptome. Cell 146: 645–658.
36. TorresTT, DolezalM, SchlottererC, OttenwalderB (2009) Expression profiling of Drosophila mitochondrial genes via deep mRNA sequencing. Nucleic Acids Res 37: 7509–7518.
37. GongWJ, GolicKG (2003) Ends-out, or replacement, gene targeting in Drosophila. Proc Natl Acad Sci U S A 100: 2556–2561.
38. RobertiM, BruniF, Loguercio PolosaP, ManzariC, GadaletaMN, et al. (2006) MTERF3, the most conserved member of the mTERF-family, is a modular factor involved in mitochondrial protein synthesis. Biochim Biophys Acta 1757: 1199–1206.
39. WangZ, CotneyJ, ShadelGS (2007) Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expression. J Biol Chem 282: 12610–12618.
40. SpahrH, SamuelssonT, HallbergBM, GustafssonCM (2010) Structure of mitochondrial transcription termination factor 3 reveals a novel nucleic acid-binding domain. Biochem Biophys Res Commun 397: 386–390.
41. ProshkinS, RahmouniAR, MironovA, NudlerE (2010) Cooperation between translating ribosomes and RNA polymerase in transcription elongation. Science 328: 504–508.
42. KondoS, BookerM, PerrimonN (2009) Cross-species RNAi rescue platform in Drosophila melanogaster. Genetics 183: 1165–1173.
43. EjsmontRK, SarovM, WinklerS, LipinskiKA, TomancakP (2009) A toolkit for high-throughput, cross-species gene engineering in Drosophila. Nat Methods 6: 435–437.
44. HuangJ, ZhouW, DongW, HongY (2009) Targeted engineering of the Drosophila genome. Fly (Austin) 3: 274–277.
45. EnriquezJA, Perez-MartosA, Lopez-PerezMJ, MontoyaJ (1996) In organello RNA synthesis system from mammalian liver and brain. Methods Enzymol 264: 50–57.
46. ShannonMF, DukeEJ (1985) Comparison of Mitochondrial and Cytoplasmic Ribosomal-Proteins in Drosophila. Comparative Biochemistry and Physiology B-Biochemistry & Molecular Biology 81: 683–686.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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