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A distinct assembly pathway of the human 39S late pre-mitoribosome.

<div class='caption-title'>Ensemble of late human 39S mitoribosome assembly intermediates.</div>
<div class='caption-title'>The immature central protuberance and DDX28 helicase in state 1.</div>
<div class='caption-title'>State 1 displays an immature PTC with GTPBB10 and MRM3 complex bound.</div>
Cheng J, Berninghausen O, Beckmann R
OpenAccess logo Nat Commun 12 4544 (2021)
Related entries: 7oi6, 7oi8, 7oi9, 7oia, 7oib, 7oic, 7oid, 7oie

Cited: 21 times
EuropePMC logo PMID: 34315873

Abstract

Assembly of the mitoribosome is largely enigmatic and involves numerous assembly factors. Little is known about their function and the architectural transitions of the pre-ribosomal intermediates. Here, we solve cryo-EM structures of the human 39S large subunit pre-ribosomes, representing five distinct late states. Besides the MALSU1 complex used as bait for affinity purification, we identify several assembly factors, including the DDX28 helicase, MRM3, GTPBP10 and the NSUN4-mTERF4 complex, all of which keep the 16S rRNA in immature conformations. The late transitions mainly involve rRNA domains IV and V, which form the central protuberance, the intersubunit side and the peptidyltransferase center of the 39S subunit. Unexpectedly, we find deacylated tRNA in the ribosomal E-site, suggesting a role in 39S assembly. Taken together, our study provides an architectural inventory of the distinct late assembly phase of the human 39S mitoribosome.

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. The Molecular and Functional Interaction Between Membrane-Bound Organelles and Membrane-Less Condensates. Zhou C. Front Cell Dev Biol 10 896305 (2022)
  5. The landscape of implantation and placentation: deciphering the function of dynamic RNA methylation at the maternal-fetal interface. Wu S, Xie H, Su Y, Jia X, Mi Y, Jia Y, Ying H. Front Endocrinol (Lausanne) 14 1205408 (2023)
  6. Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis. Antolínez-Fernández Á, Esteban-Ramos P, Fernández-Moreno MÁ, Clemente P. Front Cell Dev Biol 12 1410245 (2024)

Articles citing this publication (15)

  1. Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling. Hillen HS, Lavdovskaia E, Nadler F, Hanitsch E, Linden A, Bohnsack KE, Urlaub H, Richter-Dennerlein R. Nat Commun 12 3672 (2021)
  2. 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)
  3. 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)
  4. 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)
  5. 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)
  6. 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)
  7. Principles of mitoribosomal small subunit assembly in eukaryotes. Harper NJ, Burnside C, Klinge S. Nature 614 175-181 (2023)
  8. 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)
  9. Mitoribosome Biogenesis. Conor Moran J, Del'Olio S, Choi A, Zhong H, Barrientos A. Methods Mol Biol 2661 23-51 (2023)
  10. 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)
  11. Cryo-EM for Structure Determination of Mitochondrial Ribosome Samples. Hillen HS. Methods Mol Biol 2661 89-100 (2023)
  12. Let's make it clear: systematic exploration of mitochondrial DNA- and RNA-protein complexes by complexome profiling. Potter A, Cabrera-Orefice A, Spelbrink JN. Nucleic Acids Res 51 10619-10641 (2023)
  13. 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)
  14. 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)
  15. 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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