bims-nucpor Biomed News
on Nuclear pore complex and nucleoporins in stress, aging and disease
Issue of 2021–05–16
two papers selected by
Sara Mingu, Johannes Gutenberg University
  1. Parental genome unification is highly error-prone in mammalian embryos.
  2. TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical Cancer.
  1. Cell. 2021 Apr 30. pii: S0092-8674(21)00492-X. [Epub ahead of print]
    Parental genome unification is highly error-prone in mammalian embryos.
    Tommaso Cavazza, Yuko Takeda, Antonio Z Politi, Magomet Aushev, Patrick Aldag, Clara Baker, Meenakshi Choudhary, Jonas Bucevičius, Gražvydas Lukinavičius, Kay Elder, Martyn Blayney, Andrea Lucas-Hahn, Heiner Niemann, Mary Herbert, Melina Schuh.
      Most human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Here, we show that the parental genomes cluster with nucleoli in each pronucleus within human and bovine zygotes, and clustering is required for the reliable unification of the parental genomes after fertilization. During migration of intact pronuclei, the parental genomes polarize toward each other in a process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes on nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei, incompatible with healthy embryo development.
    Keywords:  aneuploidy; centrosomes; chromosome segregation; dynein; fertilization; genome organization; human embryo; microtubules; nuclear pore complex; spindle
    DOI:  https://doi.org/10.1016/j.cell.2021.04.013
  2. J Immunol Res. 2021 ;2021 9994004
    TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical Cancer.
    BiKang Yang, Jing Chen, YinCheng Teng.
      Far upstream element binding protein 1 (FUBP1), a DNA-binding protein, participates in diverse tumor-promoting behaviors by regulating the expression of oncogenes in the nucleus, but the underlying mechanisms remain to be elucidated. In the present study, we found that FUBP1 mRNA and protein expressions were markedly upregulated and closely linked with poor prognosis in cervical cancer. In vitro, functional experiments showed that knockdown of FUBP1 inhibited CC cell proliferation and migration. Therefore, FUBP1 plays a prooncogenic function in CC progression. Further investigations for the first time demonstrated that nuclear localization of FUBP1 regulated the gene expression of immune checkpoint NRP1. Moreover, our work demonstrated that FUBP1 translocated into the nucleus which was mediated by interacting with Transportin-1 (TNPO1). Collectively, this study revealed that FUBP1 might be a potential therapeutic target for the restriction of tumor progression.
    DOI:  https://doi.org/10.1155/2021/9994004
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