Research

The role of RNA conformations in RNA-protein recognition
RNA-proteins interactions have a key role in many biological processes. Those interactions are mediated through a variety of protein domains. The most common RNA binding domain is the RNA recognition motif (RRM). Here we studied protein-RNA structures from 9 RNA binding protein families extracted from the protein data bank (PDB). Characterizing the structural properties of RNA within the interfaces revealed that in some family, specifically in the RRM family, there is enrichment of unique RNA conformations. Looking on RNA-proteins interactions showed that the RRM domains are also enriched by interactions with nucleotides having unique RNA conformations. Further, examination of the sequences binding the RRM domain showed mainly a preference of G nucleotides in syn conformation to precede U nucleotides (not in syn conformation) and the opposite. Those findings may imply a general code of RNA recognition by the RRM domains which are able to recognize a wide variety of different RNA sequences and shapes and until now their recognition code was still unknown. Overall, this study suggests an additional recognition code of RNA-proteins, conformation readout, used only in specific protein families.
The preference of syn and C2 endo conformation in RRM-RNA interactions. (A, B, C, D, E, F, G, H) Nucleotides in syn conformation or C2 endo conformation are presented as following: Adenines are presented as red, Uridines are presented as green, Cytosines are presented as blue and Guanines are presented as yellow. Nucleotides anti or not in C2 endo involving in interactions are presented as grey. P-value indicates the statistical preference of nucleotides in syn or C2 endo conformations to be involved in interactions, between RNA and the RRM domain relative to the general abundance in all other protein-RNA interactions. (A) Frequency of hydrogen bond interactions with syn nucleotides in RNA-RRM interfaces, (B) Frequency of hydrogen bond interactions with syn nucleotides in non RNA-RRM interfaces, (C) Frequency of hydrophobic contacts interactions with syn nucleotides in RNA-RRM interfaces, (D) Frequency of hydrophobic contacts interactions with syn nucleotides in non RNA-RRM interfaces, (E) Frequency of hydrogen bond interactions with C2 endo nucleotides in RNA-RRM interfaces, (F) Frequency of hydrogen bond interactions with C2 endo nucleotides in non RNA-RRM interfaces, (G) Frequency of hydrophobic contacts interactions with C2 endo nucleotides in RNA-RRM interfaces, (H) Frequency of hydrophobic contacts interactions with C2 endo nucleotides in non RNA-RRM interfaces. (I, J) Examples of Interactions (hydrogen bonds and hydrophobic bonds) of nucleotides in rare conformations. The RNA is presented in yellow orange, the protein in sand, the hydrogen bonds as dashed black lines and the hydrophobic contacts as dashed orange lines. (I) Graphical representation of the interactions of the RRM domain with nucleotide in syn conformation (PDB ID 2LEC). Highlighted are nucleotide G -B104 (ruby), amino acid ARG - A61 (purple blue) and PHE - A59 (magenta). (J) Graphical representation of the interactions of the RRM domain with nucleotide in C2 endo conformation (PDB ID 2XS2). Highlighted are nucleotide U – B5 (ruby), amino acid LYS – A70 (purple blue) and PHE – A84 (magenta).