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Cullin-RING ubiquitin ligases (CRLs) are the largest class of ubiquitin ligases with diverse functions encompassing hundreds of cellular processes. Inactivation of core components of the CRL4 ubiquitin ligase produces a germ cell defect in Caenorhabditis elegans that is marked by abnormal globular morphology of the nucleolus and fewer germ cells. We identified DDB1 Cullin4 associated factor (DCAF)-1 as the CRL4 substrate receptor that ensures proper germ cell nucleolus morphology. We demonstrate that the dcaf-1 gene is the ncl-2 (abnormal nucleoli) gene, whose molecular identity was not previously known. We also observed that CRL4DCAF-1 is required for male tail development. Additionally, the inactivation of CRL4DCAF-1 results in a male-specific lethality in which a percentage of male progeny arrest as embryos or larvae. Analysis of the germ cell nucleolus defect using transmission electron microscopy revealed that dcaf-1 mutant germ cells possess significantly fewer ribosomes, suggesting a defect in ribosome biogenesis. We discovered that inactivation of the sperm-fate specification gene fog-1 (feminization of the germ line-1) or its protein-interacting partner, fog-3, rescues the dcaf-1 nucleolus morphology defect. Epitope-tagged versions of both FOG-1 and FOG-3 proteins are aberrantly present in adult dcaf-1(RNAi) animals, suggesting that DCAF-1 negatively regulates FOG-1 and FOG-3 expression. Murine CRL4DCAF-1 targets the degradation of the ribosome assembly factor periodic trptophan protein 1 (PWP1). We observed that the inactivation of Caenorhabditis elegansDCAF-1 increases the nucleolar levels of PWP1 in the germ line, intestine, and hypodermis. Reducing the level of PWP-1 rescues the dcaf-1 mutant defects of fewer germ cell numbers and abnormal nucleolus morphology, suggesting that the increase in PWP-1 levels contributes to the dcaf-1 germline defect. Our results suggest that CRL4DCAF-1 has an evolutionarily ancient role in regulating ribosome biogenesis including a conserved target in PWP1., Competing Interests: Conflicts of interest: The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Aberrant T cell differentiation and lymphopenia are hallmarks of severe COVID-19 disease. Since T cells must race to cull infected cells, they are quick to differentiate and achieve cytotoxic function. With this responsiveness, comes hastened apoptosis, due to a coupled mechanism of death and differentiation in both CD4+ and CD8+ lymphocytes via CD95 (Fas) and serine-threonine kinase (Akt). T cell lymphopenia in severe cases may represent cell death or peripheral migration. These facets depict SARS-Cov-2 as a lympho-manipulative pathogen; it distorts T cell function, numbers, and death, and creates a dysfunctional immune response. Whether preservation of T cells, prevention of their aberrant differentiation, and expansion of their population may alter disease course is unknown. Its investigation requires experimental interrogation of the linked differentiation and death pathway by agents known to uncouple T cell proliferation and differentiation in both CD4+ and CD8+ T cells., Competing Interests: AJL has filed a patent application pertaining to the methods described here. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Leonardi and Proenca.)

New proteins and modules have been invented throughout evolution. Gene "birth dates" in Caenorhabditis elegans range from the origins of cellular life through adaptation to a soil habitat. Possibly half are "metazoan" genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin.