The role of RNA conformation in RNA-protein recognition

Abstract

Interactions between protein and RNA play a key role in many biological processes in the gene expression pathway. Those interactions are mediated through a variety of RNA-binding protein domains, among them the highly abundant RNA recognition motif (RRM). Here we studied protein-RNA complexes from different RNA binding domain families solved by NMR and x-ray crystallography. Characterizing the structural properties of the RNA at the binding interfaces revealed an unexpected number of nucleotides with unusual RNA conformations, specifically found in RNA-RRM complexes. Moreover, we observed that the RNA nucleotides that are directly involved in interactions with the RRM domains, via hydrogen bonds and hydrophobic contacts, are significantly enriched with unique RNA conformations. Further examination of the sequences binding the RRM domain showed a preference for G nucleotides in syn conformation to precede or to follow U nucleotides in the anti-conformation, and U nucleotides in C2' endo conformation to precede U and G nucleotides possessing the more common C3' endo conformation. These findings imply a possible mode of RNA recognition by the RRM domains which enables the recognition of a wide variety of different RNA sequences and shapes. Overall, this study suggests an additional way by which the RRM domain recognizes its RNA target, involving a conformational readout.

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

“…Structural features are believed to be central for the recognition of RNA regulatory elements (RREs) by RNA binding proteins (RBPs) (65). RBPs typically do not access primary nucleotide sequence information in regions of double-stranded structure but rather recognize sequences in single-stranded regions (66).…”

A structural dissection of protein–RNA interactions based on different RNA base areas of interfaces

“…[4][5][6][7] The different structures or conformations of RNA molecules may inuence the binding protein sites. 23,28 Moreover, the base is a special part of RNA and is frequently involved in important interactions. 22,24,26,48 In the study, to qualitatively and further quantitatively measure the inuence of the RNA composition on protein-RNA interactions, we rstly proposed a new standard to distinguish protein-RNA complexes based on the percentage of the base area buried in the RNA interface area.…”

“…The hydrophobic interaction is one of the fundamental forces in the protein-nucleic acid interface. 23,63 We calculated the percent overlap between the hydrophobic and RNA-binding interfaces ( P h ) of each complex. The values are distributed between 0% and 100%, and the details are listed in ESI Table S2.…”

“…[18][19][20] In recent years, much attention has been paid to examining the general interface properties of protein-RNA complexes. [21][22][23][24][25][26][27][28] Bahadur et al 22 analyzed PRIs in terms of interface size, composition, polar interactions and atomic packing and found electrostatic complementation, base recognition and shape complementarity on the interfaces of PRIs. By investigating the preferred RNA structural states in protein-binding regions, Gupta et al 24 observed strong preferences for both RNA bases and RNA structural states in protein-RNA interactions, indicating their mutual importance in protein recognition.…”

Integrated structural biology to unravel molecular mechanisms of protein-RNA recognition

“…As such it will be difficult to predict interaction surfaces even with prior knowledge of the apo protein and RNA structures. Formation of the protein-RNA complex can involve an "induced fit" mechanism or conformational selection from a dynamic ensemble of structures that includes a pre-existing bound conformation (typically only as a minor populated species) [42,92,[100][101][102][103][104]. While an induced fit presupposes structural adaptation of at least one interaction partner, conformational selection correlates with the sampling of multiple conformers that exist in a dynamic equilibrium.…”