The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

Nucleic Acids Res. 2017 Nov 16;45(20):11989-12004. doi: 10.1093/nar/gkx852.


Prolyl isomerases are defined by a catalytic domain that facilitates the cis-trans interconversion of proline residues. In most cases, additional domains in these enzymes add important biological function, including recruitment to a set of protein substrates. Here, we report that the N-terminal basic tilted helix bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific binding to double-stranded RNA (dsRNA). This binding is selective over DNA as well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is required for its nucleolar localization and for the vast majority of its protein interactions, including those with 60S pre-ribosome and early ribosome biogenesis factors. An independent mobility of the BTHB and FKBP catalytic domains supports a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA, whereas the FKBP domain is free to interact with neighboring proteins. Apart from the identification of the BTHB as a new dsRNA-binding module, this domain adds to the growing list of auxiliary functions used by prolyl isomerases to define their primary cellular targets.

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Catalytic Domain
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Microscopy, Confocal
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Protein Binding
  • Protein Domains*
  • Protein Structure, Secondary*
  • RNA, Double-Stranded / chemistry*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Tacrolimus Binding Proteins / chemistry*
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism


  • RNA, Double-Stranded
  • FKBP3 protein, human
  • Tacrolimus Binding Proteins