Skip to main content
NCBI home page
RNA logoLink to RNA
. 1999 Feb;5(2):235–244. doi: 10.1017/s1355838299981657

Molecular dynamics studies of U1A-RNA complexes.

C M Reyes 1, P A Kollman 1
PMCID: PMC1369755  PMID: 10024175

Abstract

The U1A protein binds to a hairpin RNA and an internal-loop RNA with picomolar affinities. To probe the molecular basis of U1A binding, we performed state-of-the-art nanosecond molecular dynamics simulations on both complexes. The good agreement with experimental structures supports the protocols used in the simulations. We compare the dynamics, hydrogen-bonding occupancies, and interfacial flexibility of both complexes and also describe a rigid-body motion in the U1A-internal loop complex that is not observed in the U1A-hairpin simulation. We relate these observations to experimental mutational studies and highlight their significance in U1A binding affinity and specificity.

Full Text

The Full Text of this article is available as a PDF (266.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abola E. E., Sussman J. L., Prilusky J., Manning N. O. Protein Data Bank archives of three-dimensional macromolecular structures. Methods Enzymol. 1997;277:556–571. doi: 10.1016/s0076-6879(97)77031-9. [DOI] [PubMed] [Google Scholar]
  2. Allain F. H., Gubser C. C., Howe P. W., Nagai K., Neuhaus D., Varani G. Specificity of ribonucleoprotein interaction determined by RNA folding during complex formulation. Nature. 1996 Apr 18;380(6575):646–650. doi: 10.1038/380646a0. [DOI] [PubMed] [Google Scholar]
  3. Allain F. H., Howe P. W., Neuhaus D., Varani G. Structural basis of the RNA-binding specificity of human U1A protein. EMBO J. 1997 Sep 15;16(18):5764–5772. doi: 10.1093/emboj/16.18.5764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Auffinger P., Westhof E. Simulations of the molecular dynamics of nucleic acids. Curr Opin Struct Biol. 1998 Apr;8(2):227–236. doi: 10.1016/s0959-440x(98)80044-4. [DOI] [PubMed] [Google Scholar]
  5. Avis J. M., Allain F. H., Howe P. W., Varani G., Nagai K., Neuhaus D. Solution structure of the N-terminal RNP domain of U1A protein: the role of C-terminal residues in structure stability and RNA binding. J Mol Biol. 1996 Mar 29;257(2):398–411. doi: 10.1006/jmbi.1996.0171. [DOI] [PubMed] [Google Scholar]
  6. Birney E., Kumar S., Krainer A. R. Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res. 1993 Dec 25;21(25):5803–5816. doi: 10.1093/nar/21.25.5803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Boelens W. C., Jansen E. J., van Venrooij W. J., Stripecke R., Mattaj I. W., Gunderson S. I. The human U1 snRNP-specific U1A protein inhibits polyadenylation of its own pre-mRNA. Cell. 1993 Mar 26;72(6):881–892. doi: 10.1016/0092-8674(93)90577-d. [DOI] [PubMed] [Google Scholar]
  8. Burd C. G., Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994 Jul 29;265(5172):615–621. doi: 10.1126/science.8036511. [DOI] [PubMed] [Google Scholar]
  9. Dahl N. H., Kornstad S., Aasen G. Observasjoner i et forgiftningsmateriale under streiken ved Vinmonopolet. Tidsskr Nor Laegeforen. 1980 Jan 20;100(2):98–99. [PubMed] [Google Scholar]
  10. Eriksson M. A., Härd T., Nilsson L. Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain in complex with DNA and free in solution. Biophys J. 1995 Feb;68(2):402–426. doi: 10.1016/S0006-3495(95)80203-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fox T., Kollman P. A. The application of different solvation and electrostatic models in molecular dynamics simulations of ubiquitin: how well is the X-ray structure "maintained"? Proteins. 1996 Jul;25(3):315–334. doi: 10.1002/(SICI)1097-0134(199607)25:3<315::AID-PROT4>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  12. Gubser C. C., Varani G. Structure of the polyadenylation regulatory element of the human U1A pre-mRNA 3'-untranslated region and interaction with the U1A protein. Biochemistry. 1996 Feb 20;35(7):2253–2267. doi: 10.1021/bi952319f. [DOI] [PubMed] [Google Scholar]
  13. Hall K. B. Interaction of RNA hairpins with the human U1A N-terminal RNA binding domain. Biochemistry. 1994 Aug 23;33(33):10076–10088. doi: 10.1021/bi00199a035. [DOI] [PubMed] [Google Scholar]
  14. Hall K. B., Kranz J. K. Thermodynamics and mutations in RNA-protein interactions. Methods Enzymol. 1995;259:261–281. doi: 10.1016/0076-6879(95)59048-x. [DOI] [PubMed] [Google Scholar]
  15. Jessen T. H., Oubridge C., Teo C. H., Pritchard C., Nagai K. Identification of molecular contacts between the U1 A small nuclear ribonucleoprotein and U1 RNA. EMBO J. 1991 Nov;10(11):3447–3456. doi: 10.1002/j.1460-2075.1991.tb04909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laird-Offringa I. A., Belasco J. G. Analysis of RNA-binding proteins by in vitro genetic selection: identification of an amino acid residue important for locking U1A onto its RNA target. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11859–11863. doi: 10.1073/pnas.92.25.11859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lu J., Hall K. B. Tertiary structure of RBD2 and backbone dynamics of RBD1 and RBD2 of the human U1A protein determined by NMR spectroscopy. Biochemistry. 1997 Aug 26;36(34):10393–10405. doi: 10.1021/bi9709811. [DOI] [PubMed] [Google Scholar]
  18. Miaskiewicz K., Ornstein R. L. DNA binding by TATA-box binding protein (TBP): a molecular dynamics computational study. J Biomol Struct Dyn. 1996 Feb;13(4):593–600. doi: 10.1080/07391102.1996.10508872. [DOI] [PubMed] [Google Scholar]
  19. Miller J. L., Kollman P. A. Theoretical studies of an exceptionally stable RNA tetraloop: observation of convergence from an incorrect NMR structure to the correct one using unrestrained molecular dynamics. J Mol Biol. 1997 Jul 18;270(3):436–450. doi: 10.1006/jmbi.1997.1113. [DOI] [PubMed] [Google Scholar]
  20. Moras D., Poterszman A. RNA-protein interactions. Diverse modes of recognition. Curr Biol. 1995 Mar 1;5(3):249–251. doi: 10.1016/s0960-9822(95)00051-0. [DOI] [PubMed] [Google Scholar]
  21. Nagai K., Oubridge C., Ito N., Avis J., Evans P. The RNP domain: a sequence-specific RNA-binding domain involved in processing and transport of RNA. Trends Biochem Sci. 1995 Jun;20(6):235–240. doi: 10.1016/s0968-0004(00)89024-6. [DOI] [PubMed] [Google Scholar]
  22. Nagai K., Oubridge C., Jessen T. H., Li J., Evans P. R. Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein A. Nature. 1990 Dec 6;348(6301):515–520. doi: 10.1038/348515a0. [DOI] [PubMed] [Google Scholar]
  23. Oubridge C., Ito N., Evans P. R., Teo C. H., Nagai K. Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature. 1994 Dec 1;372(6505):432–438. doi: 10.1038/372432a0. [DOI] [PubMed] [Google Scholar]
  24. Scherly D., Kambach C., Boelens W., van Venrooij W. J., Mattaj I. W. Conserved amino acid residues within and outside of the N-terminal ribonucleoprotein motif of U1A small nuclear ribonucleoprotein involved in U1 RNA binding. J Mol Biol. 1991 Jun 20;219(4):577–584. doi: 10.1016/0022-2836(91)90651-l. [DOI] [PubMed] [Google Scholar]
  25. Tang Y., Nilsson L. Interaction of human SRY protein with DNA: a molecular dynamics study. Proteins. 1998 Jun 1;31(4):417–433. doi: 10.1002/(sici)1097-0134(19980601)31:4<417::aid-prot8>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  26. Zeng Q., Hall K. B. Contribution of the C-terminal tail of U1A RBD1 to RNA recognition and protein stability. RNA. 1997 Mar;3(3):303–314. [PMC free article] [PubMed] [Google Scholar]

Articles from RNA are provided here courtesy of The RNA Society

RESOURCES