Different low-complexity regions of SFPQ play distinct roles in the formation of biomolecular condensates

Andrew C. Marshall, Jerry Cummins, Simon Kobelke, Tianyi Zhu, Jocelyn Widagdo, Victor Anggono, Anthony Hyman, Archa H. Fox, Charles S. Bond, Mihwa Lee

Research output: Working paperPreprint


Demixing of proteins and nucleic acids into condensed liquid phases is rapidly emerging as a ubiquitous mechanism underlying the complex spatiotemporal organisation of molecules within the cell. Long disordered regions of low sequence complexity (LCRs) are a common feature of proteins that form liquid-like microscopic biomolecular condensates. In particular, RNA-binding proteins with prion-like composition have been highlighted as key drivers of liquid demixing to form condensates such as the nucleolus, paraspeckles and stress granules. Splicing factor proline- and glutamine-rich (SFPQ) is an RNA- and DNA-binding protein essential for DNA repair and paraspeckle formation. SFPQ contains two LCRs of different length and composition. Here, we show that the shorter C-terminal LCR of SFPQ is the main region responsible for the condensation of SFPQ in vitro and in the cell nucleus. In contrast, we find that, unexpectedly, the longer N-terminal prion-like LCR of SFPQ actually attenuates condensation of the full-length protein, suggesting a more regulatory role in preventing aberrant condensate formation in the cell. Our data add nuance to the emerging understanding of biomolecular condensate formation, by providing the first example of a common multifunctional nucleic acid-binding protein with an extensive prion-like region that serves to regulate rather than drive condensate formation.
Original languageEnglish
Publication statusPublished - 30 Nov 2022


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