A new role for FBP21 as regulator of Brr2 helicase activity

Nucleic Acids Res. 2017 Jul 27;45(13):7922-7937. doi: 10.1093/nar/gkx535.


Splicing of eukaryotic pre-mRNA is carried out by the spliceosome, which assembles stepwise on each splicing substrate. This requires the concerted action of snRNPs and non-snRNP accessory proteins, the functions of which are often not well understood. Of special interest are B complex factors that enter the spliceosome prior to catalytic activation and may alter splicing kinetics and splice site selection. One of these proteins is FBP21, for which we identified several spliceosomal binding partners in a yeast-two-hybrid screen, among them the RNA helicase Brr2. Biochemical and biophysical analyses revealed that an intrinsically disordered region of FBP21 binds to an extended surface of the C-terminal Sec63 unit of Brr2. Additional contacts in the C-terminal helicase cassette are required for allosteric inhibition of Brr2 helicase activity. Furthermore, the direct interaction between FBP21 and the U4/U6 di-snRNA was found to reduce the pool of unwound U4/U6 di-snRNA. Our results suggest FBP21 as a novel key player in the regulation of Brr2.

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • RNA Helicases / chemistry
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Precursors / metabolism
  • RNA Splicing
  • RNA, Small Nuclear / metabolism
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear / chemistry
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Spliceosomes / metabolism
  • Two-Hybrid System Techniques


  • Carrier Proteins
  • Nuclear Proteins
  • Peptide Fragments
  • RNA Precursors
  • RNA, Small Nuclear
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • SNRNP200 protein, human
  • Saccharomyces cerevisiae Proteins
  • U4 small nuclear RNA
  • U6 small nuclear RNA
  • WBP4 protein, human
  • RNA Helicases