Project description:Influenza virus infection damages the airways and can cause acute lung injury. Influenza virus infection remains difficult to combat since treatment is limited to supportive care or antiviral drugs to prevent influenza early in the condition. Influenza hemagglutinin (HA) is the surface glycoprotein that facilitates viral entry by binding to sialic acid-containing receptors on the host's lung cells. Therefore, it is a promising target for the development of anti-influenza therapeutic drugs. We demonstrate that the understudied E3 ligase MARCH10 destabilizes influenza HA protein in a dose-response manner and decreases the half-life of influenza HA over time. However, it does not affect the mRNA expression of influenza HA. Further, MARCH10 specifically polyubiquitinates influenza HA targeting it for degradation. When BEAS-2B cells ectopically expressed MARCH10 and were infected with PR8 virus, 1378 genes were differentially expressed. In addition, our analysis reveals that MARCH10 upregulates multiple pathways that involved interferon signaling during influenza virus infection. These findings suggest that MARCH10 plays a protective role during influenza virus infection and may enhance airway host defense and innate immunity.
Project description:During gene expression, ribosome stalling frequently occurs and can lead to detrimental effects on cellular homeostasis. Several quality control mechanisms, including RQC and NRD, have been identified to resolve these aberrant translation events. While the molecular mechanisms of each pathway have been extensively characterized, the mechanisms underlying the mutual regulation of these factors' expression remain to be elucidated. In this study, we employed a series of knockout mouse and human cell lines to investigate the crosstalk between translational quality control factors. Our findings revealed that LTN1 suppresses RNF10 expression in a manner dependent on the RING domain of LTN1. This discovery offers new insights into the coordination of translational surveillance pathways.