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Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25.
Nucleic Acids Res. 2020 Jul 01 [Online ahead of print]NA

Abstract

The mechanism for how internal ribosome entry sites (IRESs) recruit ribosomes to initiate translation of an mRNA is not completely understood. We investigated how a 40S subunit was recruited by the cricket paralysis virus intergenic region (CrPV IGR) IRES to form a stable 40S-IRES complex. Kinetic binding studies revealed that formation of the complex between the CrPV IGR and the 40S subunit consisted of two-steps: an initial fast binding step of the IRES to the 40S ribosomal subunit, followed by a slow unimolecular reaction consistent with a conformational change that stabilized the complex. We further showed that the ribosomal protein S25 (eS25), which is required by functionally and structurally diverse IRESs, impacts both steps of the complex formation. Mutations in eS25 that reduced CrPV IGR IRES activity either decreased 40S-IRES complex formation, or increased the rate of the conformational change that was required to form a stable 40S-IRES complex. Our data are consistent with a model in which eS25 facilitates initial binding of the CrPV IGR IRES to the 40S while ensuring that the conformational change stabilizing the 40S-IRES complex does not occur prematurely.

Authors+Show Affiliations

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA.Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA.Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32609821

Citation

Walters, Beth, et al. "Binding of a Viral IRES to the 40S Subunit Occurs in Two Successive Steps Mediated By ES25." Nucleic Acids Research, 2020.
Walters B, Axhemi A, Jankowsky E, et al. Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25. Nucleic Acids Res. 2020.
Walters, B., Axhemi, A., Jankowsky, E., & Thompson, S. R. (2020). Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa547
Walters B, et al. Binding of a Viral IRES to the 40S Subunit Occurs in Two Successive Steps Mediated By ES25. Nucleic Acids Res. 2020 Jul 1; PubMed PMID: 32609821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25. AU - Walters,Beth, AU - Axhemi,Armend, AU - Jankowsky,Eckhard, AU - Thompson,Sunnie R, Y1 - 2020/07/01/ PY - 2020/06/18/accepted PY - 2020/06/08/revised PY - 2019/10/25/received PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/2/medline JF - Nucleic acids research JO - Nucleic Acids Res. N2 - The mechanism for how internal ribosome entry sites (IRESs) recruit ribosomes to initiate translation of an mRNA is not completely understood. We investigated how a 40S subunit was recruited by the cricket paralysis virus intergenic region (CrPV IGR) IRES to form a stable 40S-IRES complex. Kinetic binding studies revealed that formation of the complex between the CrPV IGR and the 40S subunit consisted of two-steps: an initial fast binding step of the IRES to the 40S ribosomal subunit, followed by a slow unimolecular reaction consistent with a conformational change that stabilized the complex. We further showed that the ribosomal protein S25 (eS25), which is required by functionally and structurally diverse IRESs, impacts both steps of the complex formation. Mutations in eS25 that reduced CrPV IGR IRES activity either decreased 40S-IRES complex formation, or increased the rate of the conformational change that was required to form a stable 40S-IRES complex. Our data are consistent with a model in which eS25 facilitates initial binding of the CrPV IGR IRES to the 40S while ensuring that the conformational change stabilizing the 40S-IRES complex does not occur prematurely. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/32609821/Binding_of_a_viral_IRES_to_the_40S_subunit_occurs_in_two_successive_steps_mediated_by_eS25 L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkaa547 DB - PRIME DP - Unbound Medicine ER -
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