Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1

Nucleic Acids Res. 2022 Jan 11;50(1):522-535. doi: 10.1093/nar/gkab1216.


The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified 'β-clasp' structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Humans
  • Models, Molecular
  • Protein Conformation
  • RNA / metabolism*
  • RNA Splicing
  • RNA-Binding Proteins / metabolism*


  • DNA-Binding Proteins
  • NONO protein, human
  • PSPC1 protein, human
  • RNA-Binding Proteins
  • RNA