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Mechanism of mitoribosomal small subunit biogenesis and preinitiation.

<div class='caption-title'>Structures of pre-SSU-1 and pre-SSU-2 states.</div>
<div class='caption-title'>Structures of pre-SSU-3a,b,c states.</div>
<div class='caption-title'>Structures of pre-SSU-4, PIC-1 and IC states.</div>
Itoh Y, Khawaja A, Laptev I, Cipullo M, Atanassov I, Sergiev P, Rorbach J, Amunts A
OpenAccess logo Nature 606 603-608 (2022)
Related entries: 7pnt, 7pnu, 7pnv, 7pnw, 7pny, 7pnz, 7po0, 7po1, 7po2, 7po3, 7po4

Cited: 17 times
EuropePMC logo PMID: 35676484

Abstract

Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU-mS37-mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.

Articles - 7pnx mentioned but not cited (1)

  1. Structural insights into the specific recognition of mitochondrial ribosome-binding factor hsRBFA and 12 S rRNA by methyltransferase METTL15. Lv M, Zhou W, Hao Y, Li F, Zhang H, Yao X, Shi Y, Zhang L. Cell Discov 10 11 (2024)


Reviews citing this publication (2)

  1. GTPase Era at the heart of ribosome assembly. Gruffaz C, Smirnov A. Front Mol Biosci 10 1263433 (2023)
  2. Navigating the landscape of mitochondrial-ER communication in health and disease. Ronayne CT, Latorre-Muro P. Front Mol Biosci 11 1356500 (2024)

Articles citing this publication (14)

  1. Cryo-EM structure and rRNA modification sites of a plant ribosome. Cottilli P, Itoh Y, Nobe Y, Petrov AS, Lisón P, Taoka M, Amunts A. Plant Commun 3 100342 (2022)
  2. Principles of mitoribosomal small subunit assembly in eukaryotes. Harper NJ, Burnside C, Klinge S. Nature 614 175-181 (2023)
  3. Translation initiation of leaderless and polycistronic transcripts in mammalian mitochondria. Remes C, Khawaja A, Pearce SF, Dinan AM, Gopalakrishna S, Cipullo M, Kyriakidis V, Zhang J, Dopico XC, Yukhnovets O, Atanassov I, Firth AE, Cooperman B, Rorbach J. Nucleic Acids Res 51 891-907 (2023)
  4. Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules. Itoh Y, Singh V, Khawaja A, Naschberger A, Nguyen MD, Rorbach J, Amunts A. Elife 11 e77460 (2022)
  5. 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)
  6. Tetracyclines activate mitoribosome quality control and reduce ER stress to promote cell survival. Ronayne CT, Jackson TD, Bennett CF, Perry EA, Kantorovic N, Puigserver P. EMBO Rep 24 e57228 (2023)
  7. The recognition mode between hsRBFA and mitoribosome 12S rRNA during mitoribosomal biogenesis. Zhou W, Liu X, Lv M, Shi Y, Zhang L. Nucleic Acids Res 51 1353-1363 (2023)
  8. Yet Another Similarity between Mitochondrial and Bacterial Ribosomal Small Subunit Biogenesis Obtained by Structural Characterization of RbfA from S. aureus. Bikmullin AG, Fatkhullin B, Stetsenko A, Gabdulkhakov A, Garaeva N, Nurullina L, Klochkova E, Golubev A, Khusainov I, Trachtmann N, Blokhin D, Guskov A, Validov S, Usachev K, Yusupov M. Int J Mol Sci 24 2118 (2023)
  9. BOLA3 and NFU1 link mitoribosome iron-sulfur cluster assembly to multiple mitochondrial dysfunctions syndrome. Zhong H, Janer A, Khalimonchuk O, Antonicka H, Shoubridge EA, Barrientos A. Nucleic Acids Res 51 11797-11812 (2023)
  10. Cryo-EM for Structure Determination of Mitochondrial Ribosome Samples. Hillen HS. Methods Mol Biol 2661 89-100 (2023)
  11. 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)
  12. Mitoribosome Biogenesis. Conor Moran J, Del'Olio S, Choi A, Zhong H, Barrientos A. Methods Mol Biol 2661 23-51 (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. article-commentary Teaching old drugs new tricks. Faille A, Warren AJ. Elife 11 e84702 (2022)


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