bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2019‒05‒05
three papers selected by
Victoria Yan
Max Planck Institute of Molecular Cell Biology and Genetics


  1. Elife. 2019 Apr 30. pii: e47098. [Epub ahead of print]8
    McSwiggen DT, Hansen AS, Teves SS, Marie-Nelly H, Hao Y, Heckert AB, Umemoto KK, Dugast-Darzacq C, Tjian R, Darzacq X.
      RNA Polymerase II (Pol II) and transcription factors form concentrated hubs in cells via multivalent protein-protein interactions, often mediated by proteins with intrinsically disordered regions. During Herpes Simplex Virus infection, viral replication compartments (RCs) efficiently enrich host Pol II into membraneless domains, reminiscent of liquid-liquid phase-separation. Despite sharing several properties with phase-separated condensates, we show that RCs operate via a distinct mechanism wherein unrestricted nonspecific protein-DNA interactions efficiently outcompete host chromatin, profoundly influencing the way DNA binding proteins explore RCs. We find that the viral genome remains largely nucleosome-free, and this increase in accessibility allows Pol II and other DNA-binding proteins to repeatedly visit nearby DNA binding sites. This anisotropic behavior creates local accumulations of protein factors despite their unrestricted diffusion across RC boundaries. Our results reveal underappreciated consequences of nonspecific DNA binding in shaping gene activity, and suggest additional roles for chromatin in modulating nuclear function and organization.
    Keywords:  chromosomes; gene expression; human; molecular biophysics; structural biology; viruses
    DOI:  https://doi.org/10.7554/eLife.47098
  2. Mol Cell. 2019 May 02. pii: S1097-2765(19)30308-9. [Epub ahead of print]74(3): 413-415
    Chowdhury A, Yu M, Lemke EA.
      In this issue of Molecular Cell, Pitchiaya et al. (2019) use high-resolution single-molecule microscopy to dissect the localization of different types of RNAs with processing bodies (PBs) in cells, revealing novel insights about their dynamic recruitment to PBs.
    DOI:  https://doi.org/10.1016/j.molcel.2019.04.016
  3. Cell Immunol. 2019 Apr 17. pii: S0008-8749(19)30022-X. [Epub ahead of print]
    Sun X, Wei Y, Lee PP, Ren B, Liu C.
      Wiskott-Aldrich syndrome (WAS) is a form of primary immunodeficiency (PIDs) resulting from mutations of the gene that encodes Wiskott-Aldrich syndrome protein (WASp). WASp is the first identified and most widely studied protein belonging to the actin nucleation-promoting factor family and plays significant role in integrating and transforming signals from critical receptors on the cell surface to actin remodeling. WASp functions in immune defense and homeostasis through the regulation of actin cytoskeleton-dependent cellular processes as well as processes uncoupled with actin polymerization like nuclear transcription programs. In this article, we review the mechanisms of WASp activation through an understanding of its structure. We further discuss the role of WASp in adaptive immunity, paying special attention to some recent findings on the crucial role of WASp in the formation of immunological synapse, the regulation of T follicular helper (Tfh) cells and in the prevention of autoimmunity.
    Keywords:  Autoimmunity; BCR signaling; Follicular helper T cells; T-cell activation; Wiskott-Aldrich syndrome; Wiskott-Aldrich syndrome protein
    DOI:  https://doi.org/10.1016/j.cellimm.2019.04.007