Paper details
Trnp1 - the nuclear protein maintaining cells in a self-renewal state by co-regulating several nuclear membrane-less compartments
1 Physiological Genomics, Biomedical Center (BMC), Ludwig-Maximilians Universitaet Muenchen, 82152 Planegg/Munich, Germany
2 Institute for Stem Cell Research, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany
3 Protein Analysis Unit, BioMedical Center (BMC), Ludwig-Maximilians-Universitaet Muenchen, 82152 Planegg/Munich, Germany
4 Cell and tissue biology unit, GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium
5 CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
6 Institute of Structural Biology, Helmholtz Zentrum Muenchen, 85764 Neuherberg, Germany
7 Group Intracellular Transport and RNA Biology at the Institute of Structural Biology, Helmholtz Zentrum Muenchen, 85764, Neuherberg, Germany
8 Department of Cell Biology, BioMedical Center (BMC), Ludwig-Maximilians-Universitaet Muenchen, 82152 Planegg/Munich, Germany
9 SYNERGY, Excellence Cluster of Systems Neurology, BioMedical Center (BMC), Ludwig-Maximilians-Universitaet Muenchen, 82152 Planegg/Munich, Germany
Abstract
TMF1-regulated nuclear protein 1 (Trnp1) has been shown to exert potent roles in brain cortical development by affecting neural stem cell self-renewal and brain folding. However, its nuclear function was unknown. We showed that Trnp1 is a low complexity protein with the capacity to phase separate.
Phase separation is the mechanism that cells use to form their different membrane-less organelles such as nucleolus, nuclear speckles, and heterochromatin. We showed that Trnp1 interacts with many factors located in these nuclear membrane-less organelles co-regulating their architecture and function.
Deletion of a highly conserved small region at the N-terminus of the protein abrogates most of Trnp1 protein interactions, decreases the capacity of Trnp1 to phase separate, and abolishes its capacity to promote proliferation, indicating the importance of this small region for Trnp1 function. In summary, we identified Trnp1 as a novel co-regulator of several nuclear membrane-less compartments which functions are important to maintain cells in a self-renewing proliferative state.