RESUMO
The RIG-I receptor induces the innate antiviral responses upon sensing RNA viruses. The mechanisms through which RIG-I optimizes the strength of the downstream signaling remain incompletely understood. In this study, we identified that NSUN5 could potentiate the RIG-I innate signaling pathway. Deficiency of NSUN5 enhanced RNA virus proliferation and inhibited the induction of the downstream antiviral genes. Consistently, NSUN5-deficient mice were more susceptible to RNA virus infection than their wild-type littermates. Mechanistically, NSUN5 bound directly to both viral RNA and RIG-I, synergizing the recognition of dsRNA by RIG-I. Collectively, to our knowledge, this study characterized NSUN5 as a novel RIG-I coreceptor, playing a vital role in restricting RNA virus infection.
Assuntos
Proteína DEAD-box 58/imunologia , Metiltransferases/imunologia , Proteínas Musculares/imunologia , Infecções por Vírus de RNA/imunologia , Vírus de RNA/imunologia , RNA de Cadeia Dupla/imunologia , RNA Viral/imunologia , Receptores Imunológicos/imunologia , tRNA Metiltransferases/imunologia , Animais , Chlorocebus aethiops , Células HEK293 , Humanos , Imunidade Inata , Camundongos , Células VeroRESUMO
This study explores the relationship between the proportion of basic research investment in R&D expenditure and regional economic growth efficiency and its influence path. A panel of data from 31 China's provincial was analysed by the fixed-effects model over 2009 to 2019. Empirical results highlight that: (1) the increase in the proportion of basic research investment has a significant promoting effect on regional economic growth efficiency, but it presents an "inverted U-shaped" impact path. Meanwhile, the threshold effect model test results reveal that basic research investment plays a more significant role in promotion when the per capita income level exceeds a certain threshold. (2) The test results of the mediating effect model indicate that the improvement of the level of human capital is the intermediate channel through which the investment in basic research affects regional economic growth efficiency, while the mediating effect of the increase of knowledge storage on the process of the investment in basic research affecting regional economic growth efficiency is not supported by data. Potential policy measures are discussed.
Assuntos
Desenvolvimento Econômico , Investimentos em Saúde , Humanos , Eficiência , ChinaRESUMO
Alternative splicing of pre-mRNA increases transcriptome and proteome diversity by generating distinct isoforms that encode functionally diverse proteins, thus affecting many biological processes, including innate immunity. cGAS-STING signaling pathway, whose key molecules also undergo alternative splicing, plays a crucial role in regulating innate immunity. Protein isoforms of key components in the cGAS-STING-TBK1-IRF3 axis have been detected in a variety of species. A chain of evidence showed that these protein isoforms exhibit distinct functions compared to their normal counterparts. The mentioned isoforms act as positive or negative modulators in interferon response via distinct mechanisms. Particularly, we highlight that alternative splicing serves a vital function for the host to avoid the overactivation of the cGAS-STING signaling pathway and that viruses can utilize alternative splicing to resist antiviral response by the host. These findings could provide insights for potential alternative splicing-targeting therapeutic applications.