title: The role of RNA sequence and structure in RNA--protein interactions.
abstract: We investigate the sequence and structural properties of RNA--protein interaction sites in 211 RNA--protein chain pairs, the largest set of RNA--protein complexes analyzed to date. Statistical analysis confirms and extends earlier analyses made on smaller data sets. There are 24.6% of hydrogen bonds between RNA and protein that are nucleobase specific, indicating the importance of both nucleobase-specific and -nonspecific interactions. While there is no significant difference between RNA base frequencies in protein-binding and non-binding regions, distinct preferences for RNA bases, RNA structural states, protein residues, and protein secondary structure emerge when nucleobase-specific and -nonspecific interactions are considered separately. Guanine nucleobase and unpaired RNA structural states are significantly preferred in nucleobase-specific interactions; however, nonspecific interactions disfavor guanine, while still favoring unpaired RNA structural states. The opposite preferences of nucleobase-specific and -nonspecific interactions for guanine may explain discrepancies between earlier studies with regard to base preferences in RNA--protein interaction regions. Preferences for amino acid residues differ significantly between nucleobase-specific and -nonspecific interactions, with nonspecific interactions showing the expected bias towards positively charged residues. Irregular protein structures are strongly favored in interactions with the protein backbone, whereas there is little preference for specific protein secondary structure in either nucleobase-specific interaction or -nonspecific interaction. Overall, this study shows strong preferences for both RNA bases and RNA structural states in protein--RNA interactions, indicating their mutual importance in protein recognition.
authors.affiliation: Department of Biological Sciences, Purdue University, Hockmeyer Hall of Structural Biology, West Lafayette, IN 47907, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Gupta
authors.forename: Michael
authors.initials: M
authors.lastname: Gribskov
mesh_terms: D001483:Base Sequence; D006860:Hydrogen Bonding; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D011506:Proteins; D012313:RNA