Comparative analyses of the thermodynamic RNA binding signatures of different types of RNA recognition motifs

• Brighton Samatanga ^[2] ; Antoine Cléry ^[3] ; Pierre Barraud ^[3] ; Frédéric H-T Allain ^[3] ; Ilian Jelesarov ^[1]
  1. [1] University of Zurich

     University of Zurich

     Zürich, Suiza

     
  2. [2] Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland; Department of Biochemistry, University of Zürich, Wintherthurerstrasse 190, CH-8057 Zurich, Switzerland
  3. [3] Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland

  Mostrar afiliaciones +
• Localización: Nucleic acids research, ISSN 0305-1048, Vol. 45, Nº. 10, 2017, págs. 6037-6050
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • RNA recognition motifs (RRMs) are structurally versatile domains important in regulation of alternative splicing. Structural mechanisms of sequence-specific recognition of single-stranded RNAs (ssRNAs) by RRMs are well understood. The thermodynamic strategies are however unclear. Therefore, we utilized microcalorimetry and semi-empirical analyses to comparatively analyze the cognate ssRNA binding thermodynamics of four different RRM domains, each with a different RNA binding mode. The different binding modes are: canonical binding to the β-sheet surface; canonical binding with involvement of N- and C-termini; binding to conserved loops; and binding to an α-helix. Our results identify enthalpy as the sole and general force driving association at physiological temperatures. Also, networks of weak interactions are a general feature regulating stability of the different RRM–ssRNA complexes. In agreement, non-polyelectrolyte effects contributed between ∼75 and 90% of the overall free energy of binding in the considered complexes. The various RNA binding modes also displayed enormous heat capacity differences, that upon dissection revealed large differential changes in hydration, conformations and dynamics upon binding RNA. Altogether, different modes employed by RRMs to bind cognate ssRNAs utilize various thermodynamics strategies during the association process.