SARS-CoV-2 is the causative agent of a new type of coronavirus infection, COVID-19, which has rapidly spread worldwide. The overall genome sequence homology between SARS-CoV-2 and SARS-CoV is 79%. However, the homology of the ORF8 protein between these two coronaviruses is low, at ~26%. Previously, it has been suggested that infection by the ORF8-deleted variant of SARS-CoV-2 results in less severe symptoms than in the case of wild-type SARS-CoV-2. Although we found that ORF8 is involved in the proteasome autoimmunity system, the precise role of ORF8 in infection and pathology has not been fully clarified. In this study, we determined a new network of ORF8-interacting proteins by performing in silico analysis of the binding proteins against the previously described 47 ORF8-binding proteins. We used as a dataset 431 human protein candidates from Uniprot that physically interacted with 47 ORF8-binding proteins, as identified using STRING. Homology and phylogenetic profile analyses of the protein dataset were performed on 446 eukaryotic species whose genome sequences were available in KEGG OC. Based on the phylogenetic profile results, clustering analysis was performed using Ward's method. Our phylogenetic profiling showed that the interactors of the ORF8-interacting proteins were clustered into three classes that were conserved across chordates (Class 1: 152 proteins), metazoans (Class 2: 163 proteins), and eukaryotes (Class 3: 114 proteins). Following the KEGG pathway analysis, classification of cellular localization, tissue-specific expression analysis, and a literature study on each class of the phylogenetic profiling cluster tree, we predicted that the following: protein members in Class 1 could contribute to COVID-19 pathogenesis via complement and coagulation cascades and could promote sarcoidosis; the members of Class 1 and 2, together, may contribute to the downregulation of Interferon-β; and Class 3 proteins are associated with endoplasmic reticulum stress and the degradation of human leukocyte antigen.
The RNA polymerase II-associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in Pol II-mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO-1, RTFO-1, PAFO-1, CDC-73, and CTR-9, in Caenorhabditis elegans affects cell volume expansion of oocytes. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA-1::GFP. While four to five OMA-1::GFP-positive oocytes were observed in wild-type animals, their numbers were significantly decreased in pafo-1 mutantand leo-1(RNAi), cdc-73(RNAi), and pafo-1(RNAi) animals. Expression of a functional PAFO-1::mCherry transgene in the germline significantly rescued the oogenesis-defective phenotype of the pafo-1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA-1::GFP partially rescued the oogenesis defect in the pafo-1 mutants. Based on our findings, we propose that the PAF1C promotes oogenesis in a cell-autonomous manner by positively regulating the expression of genes involved in oocyte maturation.
The RNA polymerase II-associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in RNA polymerase II-mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO-1, RTFO-1, PAFO-1, CDC-73, and CTR-9, in Caenorhabditis elegans affects oogenesis. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA-1::GFP. While four to five OMA-1::GFP-positive oocytes were observed in wild-type animals, their numbers were significantly decreased in pafo-1 mutant and leo-1(RNAi), pafo-1(RNAi), and cdc-73(RNAi) animals. Expression of a functional PAFO-1::mCherry transgene in the germline significantly rescued the oogenesisdefective phenotype of the pafo-1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA-1::GFP partially rescued the oogenesis defect in the pafo-1 mutants.Based on our findings, we propose that the PAF1C promotes oogenesis in a cell-autonomous manner by positively regulating the expression of genes involved in oocyte maturation.
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