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Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling.

<div class='caption-title'>Structure of the MTERF4-NSUN4-bound mtLSU assembly intermediate.</div>
<div class='caption-title'>GTPBP5 cooperates with NSUN4 to mature the PTC.</div>
<div class='caption-title'>GTPBP6 binding causes rearrangements in the PTC.</div>
Hillen HS, Lavdovskaia E, Nadler F, Hanitsch E, Linden A, Bohnsack KE, Urlaub H, Richter-Dennerlein R
OpenAccess logo Nat Commun 12 3672 (2021)
Related entries: 7of0, 7of2, 7of4, 7of5, 7of6, 7of7

Cited: 26 times
EuropePMC logo PMID: 34135319

Abstract

Ribosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

Reviews citing this publication (6)

  1. Organization and expression of the mammalian mitochondrial genome. Rackham O, Filipovska A. Nat Rev Genet 23 606-623 (2022)
  2. 5-methylcytosine RNA methyltransferases and their potential roles in cancer. Li M, Tao Z, Zhao Y, Li L, Zheng J, Li Z, Chen X. J Transl Med 20 214 (2022)
  3. Types and Functions of Mitoribosome-Specific Ribosomal Proteins across Eukaryotes. Scaltsoyiannes V, Corre N, Waltz F, Giegé P. Int J Mol Sci 23 3474 (2022)
  4. Maintaining mitochondrial ribosome function: The role of ribosome rescue and recycling factors. Nadler F, Lavdovskaia E, Richter-Dennerlein R. RNA Biol 19 117-131 (2022)
  5. Mechanisms of ribosome recycling in bacteria and mitochondria: a structural perspective. Seely SM, Gagnon MG. RNA Biol 19 662-677 (2022)
  6. Nuclear and Cytoplasmatic Players in Mitochondria-Related CNS Disorders: Chromatin Modifications and Subcellular Trafficking. Gasparotto M, Lee YS, Palazzi A, Vacca M, Filippini F. Biomolecules 12 625 (2022)

Articles citing this publication (20)

  1. Structural basis for late maturation steps of the human mitoribosomal large subunit. Cipullo M, Gesé GV, Khawaja A, Hällberg BM, Rorbach J. Nat Commun 12 3673 (2021)
  2. Stepwise maturation of the peptidyl transferase region of human mitoribosomes. Lenarčič T, Jaskolowski M, Leibundgut M, Scaiola A, Schönhut T, Saurer M, Lee RG, Rackham O, Filipovska A, Ban N. Nat Commun 12 3671 (2021)
  3. Visualizing formation of the active site in the mitochondrial ribosome. Chandrasekaran V, Desai N, Burton NO, Yang H, Price J, Miska EA, Ramakrishnan V. Elife 10 e68806 (2021)
  4. Mitoribosomal small subunit maturation involves formation of initiation-like complexes. Lenarčič T, Niemann M, Ramrath DJF, Calderaro S, Flügel T, Saurer M, Leibundgut M, Boehringer D, Prange C, Horn EK, Schneider A, Ban N. Proc Natl Acad Sci U S A 119 e2114710118 (2022)
  5. Cryo-EM captures early ribosome assembly in action. Qin B, Lauer SM, Balke A, Vieira-Vieira CH, Bürger J, Mielke T, Selbach M, Scheerer P, Spahn CMT, Nikolay R. Nat Commun 14 898 (2023)
  6. Principles of mitoribosomal small subunit assembly in eukaryotes. Harper NJ, Burnside C, Klinge S. Nature 614 175-181 (2023)
  7. A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit. Rebelo-Guiomar P, Pellegrino S, Dent KC, Sas-Chen A, Miller-Fleming L, Garone C, Van Haute L, Rogan JF, Dinan A, Firth AE, Andrews B, Whitworth AJ, Schwartz S, Warren AJ, Minczuk M. Nat Commun 13 929 (2022)
  8. Lone Pair…π Contacts and Structure Signatures of r(UNCG) Tetraloops, Z-Turns, and Z-Steps: A WebFR3D Survey. Zirbel CL, Auffinger P. Molecules 27 4365 (2022)
  9. Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes. Koller TO, Turnbull KJ, Vaitkevicius K, Crowe-McAuliffe C, Roghanian M, Bulvas O, Nakamoto JA, Kurata T, Julius C, Atkinson GC, Johansson J, Hauryliuk V, Wilson DN. Nucleic Acids Res 50 11285-11300 (2022)
  10. Human mtRF1 terminates COX1 translation and its ablation induces mitochondrial ribosome-associated quality control. Nadler F, Lavdovskaia E, Krempler A, Cruz-Zaragoza LD, Dennerlein S, Richter-Dennerlein R. Nat Commun 13 6406 (2022)
  11. Miniature RNAs are embedded in an exceptionally protein-rich mitoribosome via an elaborate assembly pathway. Valach M, Benz C, Aguilar LC, Gahura O, Faktorová D, Zíková A, Oeffinger M, Burger G, Gray MW, Lukeš J. Nucleic Acids Res 51 6443-6460 (2023)
  12. Mitoribosome Biogenesis. Conor Moran J, Del'Olio S, Choi A, Zhong H, Barrientos A. Methods Mol Biol 2661 23-51 (2023)
  13. Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome. Nguyen TG, Ritter C, Kummer E. Nat Commun 14 7991 (2023)
  14. Cryo-EM for Structure Determination of Mitochondrial Ribosome Samples. Hillen HS. Methods Mol Biol 2661 89-100 (2023)
  15. Insights into the function of the chloroplastic ribosome-associated GTPase high frequency of lysogenization X in Arabidopsis thaliana. Mehrez M, Lecampion C, Ke H, Gorsane F, Field B. Plant Direct 8 e559 (2024)
  16. Mechanistic insights into the alternative ribosome recycling by HflXr. Seely SM, Basu RS, Gagnon MG. Nucleic Acids Res 52 4053-4066 (2024)
  17. Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk. Singh V, Itoh Y, Del'Olio S, Hassan A, Naschberger A, Flygaard RK, Nobe Y, Izumikawa K, Aibara S, Andréll J, Whitford PC, Barrientos A, Taoka M, Amunts A. Nat Commun 15 4272 (2024)
  18. Systematic Analysis of Assembly Intermediates in Yeast to Decipher the Mitoribosome Assembly Pathway. Del'Olio S, Barrientos A. Methods Mol Biol 2661 163-191 (2023)
  19. The zinc finger motif in the mitochondrial large ribosomal subunit protein bL36m is essential for optimal yeast mitoribosome assembly and function. Zhong H, Barrientos A. Biochim Biophys Acta Mol Cell Res 1871 119707 (2024)
  20. Y98 Mutation Leads to the Loss of RsfS Anti-Association Activity in Staphylococcus aureus. Fatkhullin B, Golubev A, Garaeva N, Validov S, Gabdulkhakov A, Yusupov M. Int J Mol Sci 23 10931 (2022)


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