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Is RsfS a Hibernation Factor or a Ribosome Biogenesis Factor?

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Abstract

Solving the structures of bacterial, archaeal, and eukaryotic ribosomes by crystallography and cryo-electron microscopy has given an impetus for studying intracellular regulatory proteins affecting various stages of protein translation. Among them are ribosome hibernation factors, which have been actively investigated during the last decade. These factors are involved in the regulation of protein biosynthesis under stressful conditions. The main role of hibernation factors is the reduction of energy consumption for protein biosynthesis and preservation of existing functional ribosomes from degradation, which increases cell survival under unfavorable conditions. Despite a broad interest in this topic, only a few articles have been published on the ribosomal silencing factor S (RsfS). According to the results of these studies, RsfS can be assigned to the group of hibernation factors. However, recent structural studies of the 50S ribosomal subunit maturation demonstrated that RsfS has the features inherent to biogenesis factors for example, ability to bind to the immature ribosomal subunit (similar to the RsfS mitochondrial ortholog MALSU1, mitochondrial assembly of ribosomal large subunit 1). In this review, we summarized the information on the function and structural features RsfS, as well as compared RsfS with MALSU1 in order to answer the emerging question on whether RsfS is a hibernation factor or a ribosome biogenesis factor. We believe that this review might promote future studies of the RsfS-involving molecular mechanisms, which so far remain completely unknown.

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Abbreviations

cryo-EM:

cryogenic electron microscopy

GTPBP:

GTP-binding protein

HPF:

hibernation promoting factor

MALSU1:

mitochondrial assembly of ribosomal large subunit 1

mt-ACP:

mitochondrial acyl carrier protein

RsfS:

ribosomal silencing factor S

References

  1. Korostelev, A., Ermolenko, D. N., and Noller, H. F. (2008) Structural dynamics of the ribosome, Curr. Opin. Chem. Biol., 12, 674-683, https://doi.org/10.1016/j.cbpa.2008.08.037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Melnikov, S., Ben-Shem, A., Garreau de Loubresse, N., Jenner, L., Yusupova, G., et al. (2012) One core, two shells: Bacterial and eukaryotic ribosomes, Nat. Struct. Mol. Biol., 19, 560-567, https://doi.org/10.1038/nsmb.2313.

    Article  CAS  PubMed  Google Scholar 

  3. Wilson, D. N., and Nierhaus, K. H. (2007) The weird and wonderful world of bacterial ribosome regulation, Crit. Rev. Biochem. Mol. Biol., 42, 187-219, https://doi.org/10.1080/10409230701360843.

    Article  CAS  PubMed  Google Scholar 

  4. Maksimova, E. M., Korepanov, A. P., Kravchenko, O. V., Baymukhametov, T. N., Myasnikov, A. G., et al. (2021) RbfA is involved in two important stages of 30S subunit assembly: Formation of the central pseudoknot and docking of Helix 44 to the decoding center, Int. J. Mol. Sci., 22, 6140, https://doi.org/10.3390/ijms22116140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Guo, Q., Goto, S., Chen, Y. L., Feng, B. Y., Xu, Y. J., et al. (2013) Dissecting the in vivo assembly of the 30S ribosomal subunit reveals the role of RimM and general features of the assembly process, Nucleic Acids Res., 41, 2609-2620, https://doi.org/10.1093/nar/gks1256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Klinge, S., and Woolford, J. L. (2019) Ribosome assembly coming into focus, Nat. Rev. Mol. Cell Biol., 20, 116-131, https://doi.org/10.1038/s41580-018-0078-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ronneau, S., and Hallez, R. (2019) Make and break the alarmone: Regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria, FEMS Microbiol. Rev., 43, 389-400, https://doi.org/10.1093/femsre/fuz009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ueta, M., Wada, C., and Wada, A. (2010) Formation of 100S ribosomes in Staphylococcus aureus by the hibernation promoting factor homolog SaHPF, Genes Cells, 15, 43-58, https://doi.org/10.1111/j.1365-2443.2009.01364.x.

    Article  CAS  PubMed  Google Scholar 

  9. Ueta, M., Wada, C., Daifuku, T., Sako, Y., Bessho, Y., et al. (2013) Conservation of two distinct types of 100S ribosome in bacteria, Genes Cells, 18, 554-574, https://doi.org/10.1111/gtc.12057.

    Article  CAS  PubMed  Google Scholar 

  10. Ueta, M., Yoshida, H., Wada, C., Baba, T., Mori, H., et al. (2005) Ribosome binding proteins YhbH and YfiA have opposite functions during 100S formation in the stationary phase of Escherichia coli, Genes Cells, 10, 1103-1112, https://doi.org/10.1111/j.1365-2443.2005.00903.x.

    Article  CAS  PubMed  Google Scholar 

  11. Ueta, M., Ohniwa, R. L., Yoshida, H., Maki, Y., Wada, C., et al. (2008) Role of HPF (hibernation promoting factor) in translational activity in Escherichia coli, J. Biochem., 143, 425-433, https://doi.org/10.1093/jb/mvm243.

    Article  CAS  PubMed  Google Scholar 

  12. Prossliner, T., Winther, K. S., Sorensen, M. A., and Gerdes, K. (2018) Ribosome hibernation, Annu. Rev. Genet., 52, 321-348, https://doi.org/10.1146/annurev-genet-120215-035130.

    Article  CAS  PubMed  Google Scholar 

  13. Han, C. D., Coe, E. H., and Martienssen, R. A. (1992) Molecular-cloning and characterization of iojap (Ij), a pattern striping gene of maize, EMBO J., 11, 4037-4046, https://doi.org/10.1002/j.1460-2075.1992.tb05497.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Galperin, M. Y., and Koonin, E. V. (2004) “Conserved hypothetical” proteins: Prioritization of targets for experimental study, Nucleic Acids Res., 32, 5452-5463, https://doi.org/10.1093/nar/gkh885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li, X., Sun, Q., Jiang, C., Yang, K., Hung, L. W., et al. (2015) Structure of ribosomal silencing factor bound to Mycobacterium tuberculosis ribosome, Structure, 23, 1858-1865, https://doi.org/10.1016/j.str.2015.07.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Basu, A., Shields, K. E., Eickhoff, C. S., Hoft, D. F., and Yap, M. N. (2018) Thermal and Nutritional regulation of ribosome hibernation in Staphylococcus aureus, J. Bacteriol., 200, e00426-18, https://doi.org/10.1128/JB.00426-18.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hauser, R., Pech, M., Kijek, J., Yamamoto, H., Titz, B., et al. (2012) RsfA (YbeB) proteins are conserved ribosomal silencing factors, PLoS Genet., 8, e1002815, https://doi.org/10.1371/journal.pgen.1002815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rorbach, J., Gammage, P. A., and Minczuk, M. (2012) C7orf30 is necessary for biogenesis of the large subunit of the mitochondrial ribosome, Nucleic Acids Res., 40, 4097-4109, https://doi.org/10.1093/nar/gkr1282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Khusainov, I., Fatkhullin, B., Pellegrino, S., Bikmullin, A., Liu, W. T., et al. (2020) Mechanism of ribosome shutdown by RsfS in Staphylococcus aureus revealed by integrative structural biology approach, Nat. Commun., 11, 1656, https://doi.org/10.1038/s41467-020-15517-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bernhardt, T. G., and de Boer, P. A. (2004) Screening for synthetic lethal mutants in Escherichia coli and identification of EnvC (YibP) as a periplasmic septal ring factor with murein hydrolase activity, Mol. Microbiol., 52, 1255-1269, https://doi.org/10.1111/j.1365-2958.2004.04063.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jiang, M., Sullivan, S. M., Walker, A. K., Strahler, J. R., Andrews, P. C., et al. (2007) Identification of novel Escherichia coli ribosome-associated proteins using isobaric tags and multidimensional protein identification techniques, J. Bacteriol., 189, 3434-3444, https://doi.org/10.1128/JB.00090-07.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Titz, B., Rajagopala, S. V., Goll, J., Hauser, R., McKevitt, M. T., et al. (2008) The binary protein interactome of Treponema pallidum – the syphilis spirochete, PLoS One, 3, e2292, https://doi.org/10.1371/journal.pone.0002292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Butland, G., Peregrin-Alvarez, J. M., Li, J., Yang, W., Yang, X., et al. (2005) Interaction network containing conserved and essential protein complexes in Escherichia coli, Nature, 433, 531-537, https://doi.org/10.1038/nature03239.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Brown, A., Rathore, S., Kimanius, D., Aibara, S., Bai, X. C., et al. (2017) Structures of the human mitochondrial ribosome in native states of assembly, Nat. Struct. Mol. Biol., 24, 866-869, https://doi.org/10.1038/nsmb.3464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jaskolowski, M., Ramrath, D. J. F., Bieri, P., Niemann, M., Mattei, S., et al. (2020) Structural insights into the mechanism of mitoribosomal large subunit biogenesis, Mol. Cell, 79, 629-644.e4, https://doi.org/10.1016/j.molcel.2020.06.030.

    Article  CAS  PubMed  Google Scholar 

  27. Basu, A., and Yap, M. N. (2017) Disassembly of the Staphylococcus aureus hibernating 100S ribosome by an evolutionarily conserved GTPase, Proc. Natl. Acad. Sci. USA, 114, E8165-E8173, https://doi.org/10.1073/pnas.1709588114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gutgsell, N. S., Deutscher, M. P., and Ofengand, J. (2005) The pseudouridine synthase RluD is required for normal ribosome assembly and function in Escherichia coli, RNA, 11, 1141-1152, https://doi.org/10.1261/rna.2550105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Charollais, J., Dreyfus, M., and Iost, I. (2004) CsdA, a cold-shock RNA helicase from Escherichia coli, is involved in the biogenesis of 50S ribosomal subunit, Nucleic Acids Res., 32, 2751-2759, https://doi.org/10.1093/nar/gkh603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Phadtare, S., and Inouye, M. (2008) The cold shock response, EcoSal Plus, 3, https://doi.org/10.1128/ecosalplus.5.4.2.

    Article  PubMed  Google Scholar 

  31. Wanschers, B. F., Szklarczyk, R., Pajak, A., van den Brand, M. A., Gloerich, J., et al. (2012) C7orf30 specifically associates with the large subunit of the mitochondrial ribosome and is involved in translation, Nucleic Acids Res., 40, 4040-4051, https://doi.org/10.1093/nar/gkr1271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fung, S., Nishimura, T., Sasarman, F., and Shoubridge, E. A. (2013) The conserved interaction of C7orf30 with MRPL14 promotes biogenesis of the mitochondrial large ribosomal subunit and mitochondrial translation, Mol. Biol. Cell, 24, 184-193, https://doi.org/10.1091/mbc.E12-09-0651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gartmann, M., Blau, M., Armache, J. P., Mielke, T., Topf, M., et al. (2010) Mechanism of eIF6-mediated inhibition of ribosomal subunit joining, J. Biol. Chem., 285, 14848-14851, https://doi.org/10.1074/jbc.C109.096057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Klinge, S., Voigts-Hoffmann, F., Leibundgut, M., Arpagaus, S., and Ban, N. (2011) Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6, Science, 334, 941-948, https://doi.org/10.1126/science.1211204.

    Article  CAS  PubMed  Google Scholar 

  35. Rathore, A., Chu, Q., Tan, D., Martinez, T. F., Donaldson, C. J., et al. (2018) MIEF1 microprotein regulates mitochondrial translation, Biochemistry, 57, 5564-5575, https://doi.org/10.1021/acs.biochem.8b00726.

    Article  CAS  PubMed  Google Scholar 

  36. Saurer, M., Ramrath, D. J. F., Niemann, M., Calderaro, S., Prange, C., et al. (2019) Mitoribosomal small subunit biogenesis in trypanosomes involves an extensive assembly machinery, Science, 365, 1144-1149, https://doi.org/10.1126/science.aaw5570.

    Article  CAS  PubMed  Google Scholar 

  37. Desai, N., Yang, H. T., Chandrasekaran, V., Kazi, R., Minczuk, M., et al. (2020) Elongational stalling activates mitoribosome-associated quality control, Science, 370, 1105-1110, https://doi.org/10.1126/science.abc7782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cipullo, M., Gese, G. V., Khawaja, A., Hallberg, B. M., and Rorbach, J. (2021) Structural basis for late maturation steps of the human mitoribosomal large subunit, Nat. Commun., 12, 3673, https://doi.org/10.1038/s41467-021-23617-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., et al. (2004) UCSF Chimera – a visualization system for exploratory research and analysis, J. Comput. Chem., 25, 1605-1612, https://doi.org/10.1002/jcc.20084.

    Article  CAS  PubMed  Google Scholar 

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Funding

The work was supported within the framework of the government task for the FRC Kazan Scientific Center, Russian Academy of Sciences.

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Authors and Affiliations

  1. Institute of Protein Research, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Bulat F. Fatkhullin & Azat G. Gabdulkhakov

  2. Institute of Genetics and Molecular and Cellular Biology, F-67400, Illkirsch-Graffenstaden, France

    Bulat F. Fatkhullin & Marat M. Yusupov

  3. Laboratory of Structural Analyze of Biomacromolecules, Federal Research Center “Kazan Scientific Center of the Russian Academy of Sciences”, 420111, Kazan, Russia

    Marat M. Yusupov

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  1. Bulat F. Fatkhullin
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  2. Azat G. Gabdulkhakov
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Correspondence to Bulat F. Fatkhullin.

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The authors declare no conflict of interest in financial or any other sphere. This article does not contain description of studies with human participants or animals performed by any of the authors.

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All figures were prepared with Chimera [42].

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Fatkhullin, B.F., Gabdulkhakov, A.G. & Yusupov, M.M. Is RsfS a Hibernation Factor or a Ribosome Biogenesis Factor?. Biochemistry Moscow 87, 500–510 (2022). https://doi.org/10.1134/S0006297922060025

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