A multi-functional nuclear protein, SFPQ: Insights into gene regulation and a subnuclear body formation — ASN Events
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  2. Session Eleven - Young Investigators Award Session
  3. A multi-functional nuclear protein, SFPQ: Insights into gene regulation and a subnuclear body formation

A multi-functional nuclear protein, SFPQ: Insights into gene regulation and a subnuclear body formation (#27)

Mihwa Lee 1 , Agata Sadowska 1 , Archa H Fox 2 , Charles S Bond 1
  1. The University of Western Australia, Crawley, WA, Australia
  2. The Western Australian Institute for Medical Research, Perth, WA, Australia

SFPQ (Splicing factor, proline- and glutamine (Q)-rich) (also known as PSF) is a multi-functional nuclear protein that has been implicated in a variety of nuclear processes including RNA biogenesis (transcription coactivation, corepression, splicing and transcriptional termination) as well as DNA repair.1  Importantly, SFPQ is a known tumour suppressor, binding to promoters of oncogenes and repressing transcription.2  A tight correlation between the expression level of SFPQ and the progression of prostate cancer has also been reported.3 

In addition to the functions described above, SFPQ also plays a key role in the structural integrity and functions of paraspeckles, subnuclear bodies implicated in the regulation of gene expression by nuclear retention of hyperedited mRNAs. SFPQ along with two other paraspeckle proteins, NONO (aka p54nrb) and PSPC1 make up the mammalian DBHS family. Following our structural studies of PSPC1 and NONO,4 we have recently solved the first structures of homodimeric SFPQ that include the entire DBHS domain. Unusual anti-parallel coiled-coil configuration in the dimer formation results in a remarkably extended structure (over 260 Å long). Crucially the structures reveal important intermolecular interactions that provide the clues on how the DBHS proteins may carry out their functions via simultaneous protein-protein and protein-nucleic acid interactions. We have also examined the effect of disrupting these interactions on the localisation of the DBHS proteins in the cell nucleus and on the DNA-binding activity of SFPQ. Implications of the interactions via extended coiled-coil domain in gene regulation and paraspeckle formation will be discussed.

  1. Shav-Tal, Y. and Zipori, D. (2002), FEBS Lett, 531: 109-14.
  2. Garen, A. and Song, X. (2008), Int J Cancer, 122: 1687-9.
  3. Berretta, R. and Moscato, P. (2010), PLoS One, 5: e12262.
  4. Passon, D.M., Lee, M., Rackham, O., Stanley, W.A., Sadowska, A., Filipovska, A., Fox, A.H., and Bond, C.S. (2012), Proc Natl Acad Sci U S A, 109: 4846-50.