Probing the structure and RNA binding of the DBHS proteins — ASN Events
  1. Schedule
  2. Session Ten - Poster Session C including Refreshments
  3. Probing the structure and RNA binding of the DBHS proteins

Probing the structure and RNA binding of the DBHS proteins (#338)

Gavin J Knott 1 , Ellen Fortini 2 , Mihwa Lee 3 , Archa H Fox 2 , Maria R Conte 4 , Charlie S Bond 1
  1. University of Western Australia, Crawley, WA, Australia
  2. Laboratory of Cancer Gene Regulation, Harry Perkins Institute of Medical Research, Perth, Western Australia , Australia
  3. La Trobe University, Melbourne , Victoria, Australia
  4. Randall Division of Cell and Molecular Biophysics, King's College London, London, UK

Paraspeckles are mammalian ribonucleoprotein bodies built on a long non-coding RNA NEAT1 that function in gene regulation1. The paraspeckle provides a distinctive window into exploring proteins and RNA involved in the molecular organisation of sub-compartments within the nucleus, particularly those involving non-coding RNAs. One such key structural and functional component of the paraspeckle are the members of the Drosophila behaviour/human splicing (DBHS) family.

In the context of gene regulation, DBHS proteins are multifunctional with roles cited in transcriptional initiation, the processing and export of RNA, maintenance of genomic DNA, nuclear pH homeostasis, neurodegeneration and carcinogenesis2. Functionally, DBHS proteins are reported to interact with a diverse range of nuclear proteins as well as single and double stranded nucleic acids. There is a growing appreciation for the fundamental significance of DBHS proteins in human health and disease.

Here we report the X-ray crystal structure of a novel DBHS homodimer refined to 2.8 Å. The structure illustrates the consistent obligatory nature of DBHS dimerisation3, while providing unique insights into dimer partner preference. Using microscale thermophoresis, we explore the preference of DBHS protein dimers for specific RNA sequences and place it in the context of their roles in gene regulation.

1.      Bond CS, Fox AH. Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol. 2009; 186: 637-44.

2.      Shav-Tal Y, Zipori D. PSF and p54(nrb)/NonO - multi-functional nuclear proteins. Febs Letters. 2002; 531: 109-14.

3.      Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, et al. Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci USA. 2012; 109:4846-50.