COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient’s death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.

SUMMARY Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic subunit of the Integrator complex, regulates transcription at these loci through its endonuclease activity. Promoters of genes require INTS11 to cleave nascent transcripts associated with paused RNAPII and induce their premature termination in the proximity of the +1 nucleosome. The turnover of RNAPII permits the subsequent recruitment of an elongation-competent RNAPII complex, leading to productive elongation. In contrast, enhancers require INTS11 catalysis not to evict paused RNAPII but rather to terminate enhancer RNA transcription beyond the +1 nucleosome. These findings are supported by the differential occupancy of negative elongation factor (NELF), SPT5, and tyrosine-1-phosphorylated RNAPII. This study elucidates the role of Integrator in mediating transcriptional elongation at human promoters through the endonucleolytic cleavage of nascent transcripts and the dynamic turnover of RNAPII.

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells’ bioenergetics differently. Tumor cells’ dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.