Trnp1 organizes diverse nuclear membrane-less compartments in neural stem cells

EMBO J. 2020 Aug 17;39(16):e103373. doi: 10.15252/embj.2019103373. Epub 2020 Jul 6.


TMF1-regulated nuclear protein 1 (Trnp1) has been shown to exert potent roles in neural development affecting neural stem cell self-renewal and brain folding, but its molecular function in the nucleus is still unknown. Here, we show that Trnp1 is a low complexity protein with the capacity to phase separate. Trnp1 interacts with factors located in several nuclear membrane-less organelles, the nucleolus, nuclear speckles, and condensed chromatin. Importantly, Trnp1 co-regulates the architecture and function of these nuclear compartments in vitro and in the developing brain in vivo. Deletion of a highly conserved region in the N-terminal intrinsic disordered region abolishes the capacity of Trnp1 to regulate nucleoli and heterochromatin size, proliferation, and M-phase length; decreases the capacity to phase separate; and abrogates most of Trnp1 protein interactions. Thus, we identified Trnp1 as a novel regulator of several nuclear membrane-less compartments, a function important to maintain cells in a self-renewing proliferative state.

Keywords: heterochromatin; mitosis; nuclear speckles; nucleolus; phase-transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division*
  • Cell Line
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Mice
  • Neural Stem Cells / metabolism*
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Protein Domains


  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Trnp1 protein, mouse