Skip to main content
Log in

Principles of amino-acid–ribonucleotide interaction revealed by binding affinities between homogeneous oligopeptides and single-stranded RNA molecules

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

We have determined the binding strengths between ribonucleotides of adenine (A), guanine (G), uracil (U), and cytosine (C) in homogeneous single-stranded ribonucleic acids (ssRNAs) and homo-decapeptides consisting of 20 common amino acids. We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions. The results provide a molecular basis for analyzing selectivity, specificity, and polymorphisms of amino-acid–ribonucleotide interactions. Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures. Pronounced favorable (such as Arg–G) and unfavorable (such as Met–U) binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions. Such interaction selectivity, specificity, and polymorphism manifest the contributions from RNA backbone, RNA bases, as well as main chain and side chain of the amino acids. Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sharp, P. A. The centrality of RNA. Cell 2009, 136, 577–580.

    Article  CAS  Google Scholar 

  2. Müller, F.; Escobar, L.; Xu, F.; Węgrzyn, E.; Nainytė, M.; Amatov, T.; Chan, C. Y.; Pichler, A.; Carell, T. A prebiotically plausible scenario of an RNA-peptide world. Nature 2022, 605, 279–284.

    Article  Google Scholar 

  3. Fire, A.; Xu, S. Q.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 391, 806–811.

    Article  CAS  Google Scholar 

  4. Mendell, J. T.; Olson, E. N. MicroRNAs in stress signaling and human disease. Cell 2012, 148, 1172–1187.

    Article  CAS  Google Scholar 

  5. He, L.; He, X. Y.; Lowe, S. W.; Hannon, G. J. MicroRNAs join the p53 network-another piece in the tumour-suppression puzzle. Nat. Rev. Cancer 2007, 7, 819–822.

    Article  CAS  Google Scholar 

  6. Medina, P. P.; Nolde, M.; Slack, F. J. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 2010, 467, 86–90.

    Article  CAS  Google Scholar 

  7. Huang, J. X.; Xiao, K. Nanoparticles-based strategies to improve the delivery of therapeutic small interfering RNA in precision oncology. Pharmaceutics 2022, 14, 1586.

    Article  CAS  Google Scholar 

  8. Yang, D. C.; Eldredge, A. C.; Hickey, J. C.; Muradyan, H.; Guan, Z. Multivalent peptide-functionalized bioreducible polymers for cellular delivery of various RNAs. Biomacromolecules 2020, 21, 1613–1624.

    Article  CAS  Google Scholar 

  9. Welch, J. J.; Swanekamp, R. J.; King, C.; Dean, D. A.; Nilsson, B. L. Functional delivery of siRNA by disulfide-constrained cyclic amphipathic peptides. ACS Med. Chem. Lett. 2016, 7, 584–589.

    Article  CAS  Google Scholar 

  10. Kim, H.; Kitamatsu, M.; Ohtsuki, T. Combined apoptotic effects of peptide and miRNA in a peptide/miRNA nanocomplex. J. Biosci. Bioeng. 2019, 128, 110–116.

    Article  CAS  Google Scholar 

  11. Berman, H. M.; Westbrook, J.; Feng, Z. K.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucl. Acids Res. 2000, 28, 235–242.

    Article  CAS  Google Scholar 

  12. Wang, X. Q.; McLachlan, J.; Zamore, P. D.; Hall, T. M. T. Modular recognition of RNA by a human pumilio-homology domain. Cell 2002, 110, 501–512.

    Article  CAS  Google Scholar 

  13. Hentze, M. W.; Castello, A.; Schwarzl, T.; Preiss, T. A brave new world of RNA-binding proteins. Nat. Rev. Mol. Cell Biol. 2018, 19, 327–341.

    Article  CAS  Google Scholar 

  14. Lee, Y. Y.; Kim, H.; Kim, V. N. Sequence determinant of small RNA production by DICER. Nature 2023, 615, 323–330.

    Article  CAS  Google Scholar 

  15. Lee, Y. Y.; Lee, H.; Kim, H.; Kim, V. N.; Roh, S. H. Structure of the human DICER-pre-miRNA complex in a dicing state. Nature 2023, 615, 331–338.

    Article  CAS  Google Scholar 

  16. Iwakawa, H. O.; Tomari, Y. Life of RISC: Formation, action, and degradation of RNA-induced silencing complex. Mol. Cell 2022, 82, 30–43.

    Article  CAS  Google Scholar 

  17. Corley, M.; Burns, M. C.; Yeo, G. W. How RNA-binding proteins interact with RNA: Molecules and mechanisms. Mol. Cell 2020, 78, 9–29.

    Article  CAS  Google Scholar 

  18. Messias, A. C.; Sattler, M. Structural basis of single-stranded RNA recognition. Acc. Chem. Res. 2004, 37, 279–287.

    Article  CAS  Google Scholar 

  19. Sharma, D.; Zagore, L. L.; Brister, M. M.; Ye, X.; Crespo-Hernández, C. E.; Licatalosi, D. D.; Jankowsky, E. The kinetic landscape of an RNA-binding protein in cells. Nature 2021, 591, 152–156.

    Article  CAS  Google Scholar 

  20. Ramanathan, M.; Porter, D. F.; Khavari, P. A. Methods to study RNA-protein interactions. Nat. Methods 2019, 16, 225–234.

    Article  CAS  Google Scholar 

  21. Krüger, D. M.; Neubacher, S.; Grossmann, T. N. Protein–RNA interactions: Structural characteristics and hotspot amino acids. RNA 2019, 24, 1457–1465.

    Article  Google Scholar 

  22. Jones, S.; Daley, D. T. A.; Luscombe, N. M.; Berman, H. M.; Thornton, J. M. Protein–RNA interactions: A structural analysis. Nucleic Acids Res. 2001, 29, 943–954.

    Article  CAS  Google Scholar 

  23. Lejeune, D.; Delsaux, N.; Charloteaux, B.; Thomas, A.; Brasseur, R. Protein-nucleic acid recognition: Statistical analysis of atomic interactions and influence of DNA structure. Proteins 2005, 61, 258–271.

    Article  CAS  Google Scholar 

  24. Auweter, S. D.; Oberstrass, F. C.; Allain, F. H. T. Sequence-specific binding of single-stranded RNA: Is there a code for recognition. Nucleic Acids Res. 2006, 34, 4943–4959.

    Article  CAS  Google Scholar 

  25. Cléry, A.; Boudet, J.; Allain, F. H. T. Single-stranded nucleic acid recognition: Is there a code after all. Structure 2013, 21, 4–6.

    Article  Google Scholar 

  26. Mirsky, A. E.; Pauling, L. On the structure of native, denatured, and coagulated proteins. Proc. Natl. Acad. Sci. USA 1936, 22, 439–447.

    Article  CAS  Google Scholar 

  27. Dill, K. A. Dominant forces in protein folding. Biochemistry 1990, 29, 7133–7155.

    Article  CAS  Google Scholar 

  28. Du, H. W.; Hu, X. Y.; Duan, H. Y.; Yu, L. L.; Qu, F. Y.; Huang, Q. X.; Zheng, W. S.; Xie, H. Y.; Peng, J. X.; Tuo, R. et al. Principles of inter-amino-acid recognition revealed by binding energies between homogeneous oligopeptides. ACS Cent. Sci. 2019, 5, 97–108.

    Article  CAS  Google Scholar 

  29. Wang, P. Y.; Fang, X. C.; Du, R.; Wang, J. L.; Liu, M. P.; Xu, P.; Li, S. Q.; Zhang, K. Y.; Ye, S. Y.; You, Q. et al. Principles of amino-acid–nucleotide interactions revealed by binding affinities between homogeneous oligopeptides and single-stranded DNA molecules. ChemBioChem 2022, 23, e202200048.

    Article  CAS  Google Scholar 

  30. Liu, J. S. Monte Carlo Strategies in Scientific Computing; Springer: New York, 2004.

    Book  Google Scholar 

  31. Wang, X. Q.; Hall, T. M. T. Structural basis for recognition of AU-rich element RNA by the HuD protein. Nat. Struct. Biol. 2001, 8, 141–145.

    Article  CAS  Google Scholar 

  32. Handa, N.; Nureki, O.; Kurimoto, K.; Kim, I.; Sakamoto, H.; Shimura, Y.; Muto, Y.; Yokoyama, S. Structural basis for recognition of the tra mRNA precursor by the sex-lethal protein. Nature 1999, 398, 579–585.

    Article  CAS  Google Scholar 

  33. Weiss, M. A.; Narayana, N. RNA recognition by arginine-rich peptide motifs. Biopolymers 1998, 48, 167–180.

    Article  CAS  Google Scholar 

  34. Baidya, N.; Uhlenbeck, O. C. The role of 2′-hydroxyl groups in an RNA–protein interaction. Biochemistry 1995, 34, 12363–12368.

    Article  CAS  Google Scholar 

  35. Calnan, B. J.; Tidor, B.; Biancalana, S.; Hudson, D.; Frankel, A. D. Arginine-mediated RNA recognition: The arginine fork. Science 1991, 252, 1167–1171.

    Article  CAS  Google Scholar 

  36. Chavali, S. S.; Cavender, C. E.; Mathews, D. H.; Wedekind, J. E. Arginine forks are a widespread motif to recognize phosphate backbones and guanine nucleobases in the RNA major groove. J. Am. Chem. Soc. 2020, 142, 19835–19839.

    Article  CAS  Google Scholar 

  37. Levintov, L.; Vashisth, H. Role of salt–bridging interactions in recognition of viral RNA by arginine-rich peptides. Biophys. J. 2021, 120, 5060–5073.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 21721002, 32101130, and 31971295). Financial support from the Strategic Priority Research Program of Chinese Academy of Sciences (No. XDB36000000) is also gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yanlian Yang or Chen Wang.

Electronic supplementary material

12274_2023_5971_MOESM1_ESM.pdf

Electronic Supplementary Material: Principles of amino-acid–ribonucleotide interaction revealed by binding affinities between homogeneous oligopeptides and single-stranded RNA molecules

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, P., Fang, X., Li, P. et al. Principles of amino-acid–ribonucleotide interaction revealed by binding affinities between homogeneous oligopeptides and single-stranded RNA molecules. Nano Res. 16, 13294–13300 (2023). https://doi.org/10.1007/s12274-023-5971-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-023-5971-9

Keywords

Navigation