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Mitoribosome Biogenesis

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The Mitoribosome

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2661))

Abstract

Mitoribosome biogenesis is a complex and energetically costly process that involves RNA elements encoded in the mitochondrial genome and mitoribosomal proteins most frequently encoded in the nuclear genome. The process is catalyzed by extra-ribosomal proteins, nucleus-encoded assembly factors that act in all stages of the assembly process to coordinate the processing and maturation of ribosomal RNAs with the hierarchical association of ribosomal proteins. Biochemical studies and recent cryo-EM structures of mammalian mitoribosomes have provided hints regarding their assembly. In this general concept chapter, we will briefly describe the current knowledge, mainly regarding the mammalian mitoribosome biogenesis pathway and factors involved, and will emphasize the biological sources and approaches that have been applied to advance the field.

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References

  1. Küntzel H, Noll H (1967) Mitochondrial and cytoplasmic polysomes from Neurospora crassa. Nature 215(5108):1340–1345. https://doi.org/10.1038/2151340a0

    Article  PubMed  Google Scholar 

  2. O’Brien TW, Kalf GF (1967) Ribosomes from rat liver mitochondria. I. Isolation procedure and contamination studies. J Biol Chem 242(9):2172–2179

    Article  PubMed  Google Scholar 

  3. O’Brien TW, Kalf GF (1967) Ribosomes from rat liver mitochondira. II. Partial characterization. J Biol Chem 242(9):2180–2185

    Article  PubMed  Google Scholar 

  4. Zeng R, Smith E, Barrientos A (2018) Yeast mitoribosome large subunit assembly proceeds by hierarchical incorporation of protein clusters and modules on the inner membrane. Cell Metab 27(3):645–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bogenhagen DF, Ostermeyer-Fay AG, Haley JD et al (2018) Kinetics and mechanism of mammalian mitochondrial ribosome assembly. Cell Rep 22(7):1935–1944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Amunts A, Brown A, Bai X et al (2014) Structure of the yeast mitochondrial large ribosomal subunit. Science 343:1485–1489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Desai N, Brown A, Amunts A et al (2017) The structure of the yeast mitochondrial ribosome. Science 355(6324):528–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lenarčič T, Niemann M, Ramrath DJF et al (2022) Mitoribosomal small subunit maturation involves formation of initiation-like complexes. Proc Natl Acad Sci U S A 119(3). https://doi.org/10.1073/pnas.2114710118

  9. Tobiasson V, Gahura O, Aibara S et al (2021) Interconnected assembly factors regulate the biogenesis of mitoribosomal large subunit. EMBO J 40(6):e106292. https://doi.org/10.15252/embj.2020106292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Soufari H, Waltz F, Parrot C et al (2020) Structure of the mature kinetoplastids mitoribosome and insights into its large subunit biogenesis. Proc Natl Acad Sci U S A 117(47):29851–29861. https://doi.org/10.1073/pnas.2011301117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Saurer M, Ramrath DJF, Niemann M et al (2019) Mitoribosomal small subunit biogenesis in trypanosomes involves an extensive assembly machinery. Science 365(6458):1144–1149

    Article  CAS  PubMed  Google Scholar 

  12. Greber BJ, Bieri P, Leibundgut M et al (2015) Ribosome. The complete structure of the 55S mammalian mitochondrial ribosome. Science 348(6232):303–308

    Article  CAS  PubMed  Google Scholar 

  13. Greber BJ, Boehringer D, Leibundgut M et al (2014) The complete structure of the large subunit of the mammalian mitochondrial ribosome. Nature 515(7526):283–286

    Article  CAS  PubMed  Google Scholar 

  14. Amunts A, Brown A, Toots J et al (2015) The structure of the human mitochondrial ribosome. Science 348(6230):95–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brown A, Amunts A, Bai XC et al (2014) Structure of the large ribosomal subunit from human mitochondria. Science 346(6210):718–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Aibara S, Singh V, Modelska A et al (2020) Structural basis of mitochondrial translation. Elife 9. https://doi.org/10.7554/eLife.58362

  17. Brown A, Rathore S, Kimanius D et al (2017) Structures of the human mitochondrial ribosome in native states of assembly. Nat Struct Mol Biol 24(10):866–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Itoh Y, Khawaja A, Laptev I et al (2022) Mechanism of mitoribosomal small subunit biogenesis and preinitiation. Nature 606(7914):603–608. https://doi.org/10.1038/s41586-022-04795-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cheng J, Berninghausen O, Beckmann R (2021) A distinct assembly pathway of the human 39S late pre-mitoribosome. Nat Commun 12(1):4544. https://doi.org/10.1038/s41467-021-24818-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cipullo M, Gesé GV, Khawaja A et al (2021) Structural basis for late maturation steps of the human mitoribosomal large subunit. Nat Commun 12(1):3673. https://doi.org/10.1038/s41467-021-23617-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hillen HS, Lavdovskaia E, Nadler F et al (2021) Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling. Nat Commun 12(1):3672. https://doi.org/10.1038/s41467-021-23702-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lenarčič T, Jaskolowski M, Leibundgut M et al (2021) Stepwise maturation of the peptidyl transferase region of human mitoribosomes. Nat Commun 12(1):3671. https://doi.org/10.1038/s41467-021-23811-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chandrasekaran V, Desai N, Burton NO et al (2021) Visualizing formation of the active site in the mitochondrial ribosome. Elife 10. https://doi.org/10.7554/eLife.68806

  24. Smits P, Smeitink JA, van den Heuvel LP et al (2007) Reconstructing the evolution of the mitochondrial ribosomal proteome. Nucleic Acids Res 35(14):4686–4703. https://doi.org/10.1093/nar/gkm441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Petrov AS, Wood EC, Bernier CR et al (2019) Structural patching fosters divergence of mitochondrial ribosomes. Mol Biol Evol 36(2):207–219

    Article  CAS  PubMed  Google Scholar 

  26. van der Sluis EO, Bauerschmitt H, Becker T et al (2015) Parallel structural evolution of mitochondrial ribosomes and OXPHOS complexes. Genome Biol Evol 7(5):1235–1251. https://doi.org/10.1093/gbe/evv061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. De Silva D, Fontanesi F, Barrientos A (2013) The DEAD-Box protein Mrh4 functions in the assembly of the mitochondrial large ribosomal subunit. Cell Metab 18:712–725

    Article  PubMed  Google Scholar 

  28. Maiti P, Kim HJ, Tu YT et al (2018) Human GTPBP10 is required for mitoribosome maturation. Nucleic Acids Res 13. https://doi.org/10.1093/nar/gky938

  29. Ferrari A, Del’Olio S, Barrientos A (2021) The diseased mitoribosome. FEBS Lett 595(8):1025–1061. https://doi.org/10.1002/1873-3468.14024

    Article  CAS  PubMed  Google Scholar 

  30. Maiti P, Lavdovskaia E, Barrientos A et al (2020) Role of GTPases in driving mitoribosome assembly. Trends Cell Biol 3(4):284–297

    Article  Google Scholar 

  31. Lopez Sanchez MIG, Krüger A, Shiriaev DI et al (2021) Human mitoribosome biogenesis and its emerging links to disease. Int J Mol Sci 22(8). https://doi.org/10.3390/ijms22083827

  32. Kummer E, Ban N (2021) Mechanisms and regulation of protein synthesis in mitochondria. Nat Rev Mol Cell Biol 22(5):307–325. https://doi.org/10.1038/s41580-021-00332-2

    Article  CAS  PubMed  Google Scholar 

  33. Lavdovskaia E, Hillen HS, Richter-Dennerlein R (2022) Hierarchical folding of the catalytic core during mitochondrial ribosome biogenesis. Trends Cell Biol 32(3):182–185. https://doi.org/10.1016/j.tcb.2021.09.004

    Article  CAS  PubMed  Google Scholar 

  34. Kummer E, Leibundgut M, Rackham O et al (2018) Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM. Nature 560(7717):263–267

    Article  CAS  PubMed  Google Scholar 

  35. Singh V, Itoh Y, Huynen MA et al (2022) Activation mechanism of mitochondrial translation by LRPPRC-SLIRP. bioRxiv:2022.2006.2020.496763. https://doi.org/10.1101/2022.06.20.496763

  36. Chen Y, Hagopian K, Bibus D et al (2013) The influence of dietary lipid composition on liver mitochondria from mice following 1 month of calorie restriction. Biosci Rep 33(1):83–95. https://doi.org/10.1042/BSR20120060

    Article  CAS  Google Scholar 

  37. Singh V, Itoh I, Del’Olio S et al (2023) The complete structure of human mitoribosome, roles of mito-specific protein elements, cofactors and rRNA modifications. Nat Commun In press

    Google Scholar 

  38. Greber BJ, Ban N (2016) Structure and function of the mitochondrial ribosome. Annu Rev Biochem 85:103–132

    Article  CAS  PubMed  Google Scholar 

  39. Itoh Y, Singh V, Khawaja A, Naschberger A, Nguyen MD, Rorbach J, Amunts A (2022) Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules. eLife 11:e77460

    Google Scholar 

  40. Yusupova GZ, Yusupov MM, Cate JH et al (2001) The path of messenger RNA through the ribosome. Cell 106(2):233–241. https://doi.org/10.1016/s0092-8674(01)00435-4

    Article  CAS  PubMed  Google Scholar 

  41. Takyar S, Hickerson RP, Noller HF (2005) mRNA helicase activity of the ribosome. Cell 120:49–58

    Article  CAS  PubMed  Google Scholar 

  42. Helm M, Brulé H, Friede D et al (2000) Search for characteristic structural features of mammalian mitochondrial tRNAs. RNA 6(10):1356–1379. https://doi.org/10.1017/s1355838200001047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rorbach J, Gao F, Powell CA et al (2016) Human mitochondrial ribosomes can switch their structural RNA composition. Proc Natl Acad Sci U S A 113(43):12198–12201. https://doi.org/10.1073/pnas.1609338113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Greber BJ, Boehringer D, Leitner A et al (2014) Architecture of the large subunit of the mammalian mitochondrial ribosome. Nature 505(7484):515–519. https://doi.org/10.1038/nature12890

    Article  CAS  PubMed  Google Scholar 

  45. Antonicka H, Choquet K, Lin ZY et al (2017) A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep 18(1):28–38

    Article  CAS  PubMed  Google Scholar 

  46. Rackham O, Busch JD, Matic S et al (2016) Hierarchical RNA processing is required for mitochondrial ribosome assembly. Cell Rep 16(7):1874–1890

    Article  CAS  PubMed  Google Scholar 

  47. Lee KW, Bogenhagen DF (2014) Assignment of 2′-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16 S ribosomal RNA (rRNA). J Biol Chem 289(36):24936–24942. https://doi.org/10.21074/jbc.C24114.581868. Epub 582014 Jul 581829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rorbach J, Boesch P, Gammage PA et al (2014) MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome. Mol Biol Cell 9:01–0014

    Google Scholar 

  49. Jaskolowski M, Ramrath DJF, Bieri P et al (2020) Structural insights into the mechanism of mitoribosomal large subunit biogenesis. Mol Cell 79(4):629–644

    Article  CAS  PubMed  Google Scholar 

  50. Chen SS, Williamson JR (2013) Characterization of the ribosome biogenesis landscape in E. coli using quantitative mass spectrometry. J Mol Biol 425(4):767–779

    Article  CAS  PubMed  Google Scholar 

  51. Davis JH, Tan YZ, Carragher B et al (2016) Modular assembly of the bacterial large ribosomal subunit. Cell 167(6):1610–1622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Snider J, Wang D, Bogenhagen DF et al (2019) Pulse SILAC approaches to the measurement of cellular dynamics. Adv Exp Med Biol 1140:575–583. https://doi.org/10.1007/978-3-030-15950-4_34

    Article  CAS  PubMed  Google Scholar 

  53. Lindahl L (1975) Intermediates and time kinetics of the in vivo assembly of Escherichia coli ribosomes. J Mol Biol 92(1):15–37

    Article  CAS  PubMed  Google Scholar 

  54. Davis JH, Williamson JR (2017) Structure and dynamics of bacterial ribosome biogenesis. Philos Trans R Soc Lond Ser B Biol Sci 372(1716). https://doi.org/10.1098/rstb.2016.0181

  55. Antonicka H, Sasarman F, Nishimura T et al (2013) The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression. Cell Metab 17(3):386–398

    Article  CAS  PubMed  Google Scholar 

  56. Jourdain AA, Koppen M, Wydro M et al (2013) GRSF1 regulates RNA processing in mitochondrial RNA granules. Cell Metab 17(3):399–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Antonicka H, Shoubridge EA (2015) Mitochondrial RNA granules are centers for posttranscriptional RNA processing and ribosome biogenesis. Cell Rep 10(6):920–932

    Article  CAS  PubMed  Google Scholar 

  58. Tu YT, Barrientos A (2015) The human mitochondrial DEAD-box protein DDX28 resides in RNA granules and functions in mitoribosome assembly. Cell Rep 10(6):854–864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shajani Z, Sykes MT, Williamson JR (2011) Assembly of bacterial ribosomes. Annu Rev Biochem 80:501–526

    Article  CAS  PubMed  Google Scholar 

  60. Britton RA (2009) Role of GTPases in bacterial ribosome assembly. Annu Rev Microbiol 63:155–176

    Article  CAS  PubMed  Google Scholar 

  61. Barrientos A, Korr D, Barwell KJ et al (2003) MTG1 codes for a conserved protein required for mitochondrial translation. Mol Biol Cell 14(6):2292–2302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Paul MF, Alushin GM, Barros MH et al (2012) The putative GTPase encoded by MTG3 functions in a novel pathway for regulating assembly of the small subunit of yeast mitochondrial ribosomes. J Biol Chem 287(29):24346–24355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dennerlein S, Rozanska A, Wydro M et al (2010) Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit. Biochem J 430(3):551–558

    Article  CAS  PubMed  Google Scholar 

  64. Metodiev MD, Spahr H, Loguercio Polosa P et al (2014) NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet 10(2):e1004110

    Article  PubMed  PubMed Central  Google Scholar 

  65. De Silva D, Poliquin S, Zeng R et al (2017) The DEAD-box helicase Mss116 plays distinct roles in mitochondrial ribogenesis and mRNA-specific translation. Nucleic Acids Res 45(11):6628–6643

    Article  PubMed  PubMed Central  Google Scholar 

  66. Dalla Rosa I, Durigon R, Pearce SF et al (2014) MPV17L2 is required for ribosome assembly in mitochondria. Nucleic Acids Res 42(13):8500–8515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. De Silva D, Tu YT, Amunts A et al (2015) Mitochondrial ribosome assembly in health and disease. Cell Cycle 14(14):2226–2250

    Article  PubMed  PubMed Central  Google Scholar 

  68. Boczonadi V, Horvath R (2014) Mitochondria: impaired mitochondrial translation in human disease. Int J Biochem Cell Biol 48(100):77–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gopisetty G, Thangarajan R (2016) Mammalian mitochondrial ribosomal small subunit (MRPS) genes: a putative role in human disease. Gene 589(1):27–35

    Article  CAS  PubMed  Google Scholar 

  70. Pulman J, Ruzzenente B, Bianchi L et al (2019) Mutations in the MRPS28 gene encoding the small mitoribosomal subunit protein bS1m in a patient with intrauterine growth retardation, craniofacial dysmorphism and multisystemic involvement. Hum Mol Genet 28(9):1445–1462

    Google Scholar 

  71. Bugiardini E, Mitchell AL, Rosa ID et al (2019) MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy. Hum Mol Genet 28(16):2711–2719

    Google Scholar 

  72. Borna NN, Kishita Y, Kohda M et al (2019) Mitochondrial ribosomal protein PTCD3 mutations cause oxidative phosphorylation defects with Leigh syndrome. Neurogenetics 20(1):9–25

    Article  CAS  PubMed  Google Scholar 

  73. Di Nottia M, Marchese M, Verrigni D et al (2020) A homozygous MRPL24 mutation causes a complex movement disorder and affects the mitoribosome assembly. Neurobiol Dis 141:104880

    Article  PubMed  Google Scholar 

  74. Gardeitchik T, Mohamed M, Ruzzenente B et al (2018) Bi-allelic mutations in the mitochondrial ribosomal protein MRPS2 cause sensorineural hearing loss, hypoglycemia, and multiple OXPHOS complex deficiencies. Am J Hum Genet 102(4):685–695. https://doi.org/10.1016/j.ajhg.2018.1002.1012. Epub 2018 Mar 1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. O’Brien TW, O’Brien BJ, Norman RA (2005) Nuclear MRP genes and mitochondrial disease. Gene 354:147–151

    Article  PubMed  Google Scholar 

  76. Saada A, Shaag A, Arnon S et al (2007) Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. J Med Genet 44(12):784–786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Emdadul Haque M, Grasso D, Miller C et al (2008) The effect of mutated mitochondrial ribosomal proteins S16 and S22 on the assembly of the small and large ribosomal subunits in human mitochondria. Mitochondrion 8(3):254–261

    Article  CAS  PubMed  Google Scholar 

  78. Rebelo-Guiomar P, Pellegrino S, Dent KC et al (2022) A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit. Nat Commun 13(1):929. https://doi.org/10.1038/s41467-022-28503-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Klinge S, Woolford JL Jr (2019) Ribosome assembly coming into focus. Nat Rev Mol Cell Biol 20(2):116–131. https://doi.org/10.1038/s41580-018-0078-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Srivastava AK, Schlessinger D (1990) Mechanism and regulation of bacterial ribosomal RNA processing. Annu Rev Microbiol 44:105–129. https://doi.org/10.1146/annurev.mi.44.100190.000541

    Article  CAS  PubMed  Google Scholar 

  81. Montoya J, Christianson T, Levens D et al (1982) Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA. Proc Natl Acad Sci U S A 79(23):7195–7199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Terzioglu M, Ruzzenente B, Harmel J 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(4):618–626. https://doi.org/10.1016/j.cmet.2013.03.006

    Article  CAS  PubMed  Google Scholar 

  83. Litonin D, Sologub M, Shi Y 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(24):18129–18133. https://doi.org/10.1074/jbc.C110.128918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Siira SJ, Rossetti G, Richman TR et al (2018) Concerted regulation of mitochondrial and nuclear non-coding RNAs by a dual-targeted RNase Z. EMBO Rep 19(10). https://doi.org/10.15252/embr.201846198

  85. Jedynak-Slyvka M, Jabczynska A, Szczesny RJ (2021) Human mitochondrial RNA processing and modifications: overview. Int J Mol Sci 22(15). https://doi.org/10.3390/ijms22157999

  86. Uchiumi T, Ohgaki K, Yagi M et al (2010) ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation. Nucleic Acids Res 38(16):5554–5568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Seidel-Rogol BL, McCulloch V, Shadel GS (2003) Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop. Nat Genet 33(1):23–24

    Article  CAS  PubMed  Google Scholar 

  88. Szczepanowska K, Maiti P, Kukat A et al (2016) CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels. EMBO J 35(23):2566–2583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Summer S, Smirnova A, Gabriele A et al (2020) YBEY is an essential biogenesis factor for mitochondrial ribosomes. Nucleic Acids Res 48(17):9762–9786. https://doi.org/10.1093/nar/gkaa148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kolanczyk M, Pech M, Zemojtel T et al (2011) NOA1 is an essential GTPase required for mitochondrial protein synthesis. Mol Biol Cell 22(1):1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. He J, Cooper HM, Reyes A et al (2012) Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit. Nucleic Acids Res 40:6097–6108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Reyes A, Favia P, Vidoni S et al (2020) RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. PLoS Genet 16(7):e1008923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Van Haute L, Hendrick AG, D’Souza AR et al (2019) METTL15 introduces N4-methylcytidine into human mitochondrial 12S rRNA and is required for mitoribosome biogenesis. Nucleic Acids Res 47(19):10267–10281. https://doi.org/10.1093/nar/gkz735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Fung S, Nishimura T, Sasarman F et al (2013) The conserved interaction of C7orf30 with MRPL14 promotes biogenesis of the mitochondrial large ribosomal subunit and mitochondrial translation. Mol Biol Cell 24(3):184–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rorbach J, Gammage PA, Minczuk M (2012) C7orf30 is necessary for biogenesis of the large subunit of the mitochondrial ribosome. Nucleic Acids Res 40:4097–4109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Popow J, Alleaume AM, Curk T et al (2015) FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation. RNA 21(11):1873–1884. https://doi.org/10.1261/rna.052365.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kim H-J, Barrientos A (2018) MTG1 couples mitoribosome large subunit assembly and intersubunit bridge formation. Nucleic Acid Res 46:8435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Maiti P, Antonicka H, Gingras A-C et al (2020) Human GTPBP5 (MTG2) fuels mitoribosome large subunit maturation by facilitating 16S rRNA methylation. Nucleic Acids Res 48(14):7924–7943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lee KW, Okot-Kotber C, Lacomb JF et al (2013) Mitochondrial rRNA methyltransferase family members are positioned to modify nascent rRNA in foci near the mtDNA nucleoid. J Biol Chem 288(43):31386–31399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Nikolay R, Hilal T, Schmidt S et al (2021) Snapshots of native pre-50S ribosomes reveal a biogenesis factor network and evolutionary specialization. Mol Cell 81(6):1200–1215.e1209. https://doi.org/10.1016/j.molcel.2021.02.006

    Article  CAS  PubMed  Google Scholar 

  101. Zaganelli S, Rebelo-Guiomar P, Maundrell K et al (2017) The pseudouridine synthase RPUSD4 is an essential component of mitochondrial RNA granules. J Biol Chem 292(11):4519–4532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Lavdovskaia E, Denks K, Nadler F et al (2020) Dual function of GTPBP6 in biogenesis and recycling of human mitochondrial ribosomes. Nucleic Acids Res. https://doi.org/10.1093/nar/gkaa1132

  103. Kim HJ, Maiti P, Barrientos A (2017) Mitochondrial ribosomes in cancer. Semin Cancer Biol 47:67–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Ban N, Beckmann R, Cate JH et al (2014) A new system for naming ribosomal proteins. Curr Opin Struct Biol 24:165–169. https://doi.org/10.1016/j.sbi.2014.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Metodiev MD, Lesko N, Park CB 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(4):386–397

    Article  CAS  PubMed  Google Scholar 

  106. Liu X, Shen S, Wu P et al (2019) Structural insights into dimethylation of 12S rRNA by TFB1M: indispensable role in translation of mitochondrial genes and mitochondrial function. Nucleic Acids Res 47(14):7648–7665. https://doi.org/10.1093/nar/gkz505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Powell CA, Minczuk M (2020) TRMT2B is responsible for both tRNA and rRNA m(5)U-methylation in human mitochondria. RNA Biol 17(4):451–462. https://doi.org/10.1080/15476286.2020.1712544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Laptev I, Shvetsova E, Levitskii S et al (2020) Mouse Trmt2B protein is a dual specific mitochondrial metyltransferase responsible for m(5)U formation in both tRNA and rRNA. RNA Biol 17(4):441–450. https://doi.org/10.1080/15476286.2019.1694733

    Article  CAS  PubMed  Google Scholar 

  109. Shi Z, Xu S, Xing S et al (2019) Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes. FASEB J 33(11):13040–13050. https://doi.org/10.1096/fj.201901331R

    Article  CAS  PubMed  Google Scholar 

  110. Tang T, Zheng B, Chen SH et al (2009) hNOA1 interacts with complex I and DAP3 and regulates mitochondrial respiration and apoptosis. J Biol Chem 284(8):5414–5424. https://doi.org/10.1074/jbc.M807797200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bar-Yaacov D, Frumkin I, Yashiro Y et al (2016) Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates. PLoS Biol 14(9):e1002557. https://doi.org/10.1371/journal.pbio.1002557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Arroyo JD, Jourdain AA, Calvo SE et al (2016) A genome-wide CRISPR death screen identifies genes essential for oxidative phosphorylation. Cell Metab 24(6):875–885. https://doi.org/10.1016/j.cmet.2016.08.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Rathore A, Chu Q, Tan D et al (2018) MIEF1 microprotein regulates mitochondrial translation. Biochemistry 57(38):5564–5575

    Article  CAS  PubMed  Google Scholar 

  114. Dibley MG, Formosa LE, Lyu B et al (2020) The mitochondrial acyl-carrier protein interaction network highlights important roles for LYRM family members in complex i and mitoribosome assembly. Mol Cell Proteomics 19(1):65–77. https://doi.org/10.1074/mcp.RA119.001784

    Article  CAS  PubMed  Google Scholar 

  115. Wredenberg A, Lagouge M, Bratic A et al (2013) MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals. PLoS Genet 9(1):e1003178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Camara Y, Asin-Cayuela J, Park CB et al (2011) MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome. Cell Metab 13(5):527–539

    Article  CAS  PubMed  Google Scholar 

  117. Fogal V, Richardson AD, Karmali PP et al (2010) Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation. Mol Cell Biol 30(6):1303–1318. https://doi.org/10.1128/mcb.01101-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Yagi M, Uchiumi T, Takazaki S et al (2012) p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability. Nucleic Acids Res 40(19):9717–9737. https://doi.org/10.1093/nar/gks774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This research was supported by an NIGMS-MIRA award [R35GM118141 to A.B.] and an NICHD F30 predoctoral M.D./Ph.D. fellowship [F30HD107939 to J.C.M.].

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  1. J. Conor Moran and Samuel Del’Olio contributed equally with all other contributors.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Miami, Miller School of Medicine, Miami, FL, USA

    J. Conor Moran & Hui Zhong

  2. Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, FL, USA

    Samuel Del’Olio

  3. Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL, USA

    Austin Choi

  4. Department of Neurology and Department of Biochemistry and Molecular Biology, University of Miami, Miller School of Medicine, Miami, FL, USA

    Antoni Barrientos

Authors
  1. J. Conor Moran
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  2. Samuel Del’Olio
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  3. Austin Choi
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  4. Hui Zhong
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  5. Antoni Barrientos
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Corresponding author

Correspondence to Antoni Barrientos .

Editor information

Editors and Affiliations

  1. Miller School of Medicine, University of Miami, Miami, FL, USA

    Antoni Barrientos

  2. Miller School of Medicine, University of Miami, Miami, FL, USA

    Flavia Fontanesi

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Conor Moran, J., Del’Olio, S., Choi, A., Zhong, H., Barrientos, A. (2023). Mitoribosome Biogenesis. In: Barrientos, A., Fontanesi, F. (eds) The Mitoribosome. Methods in Molecular Biology, vol 2661. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3171-3_3

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  • DOI: https://doi.org/10.1007/978-1-0716-3171-3_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3170-6

  • Online ISBN: 978-1-0716-3171-3

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