本研究运用RT-PCR技术,首次从大熊猫(Ailuropoda melanoleuca)的肌肉组织总RNA中成功克隆了RPS24(Ribosomal Protein S24)基因的表达序列,并对其进行了测序及初步分析.结果表明:大熊猫RPS24基因的表达序列全长为431bp,开放阅读框(ORF)为...本研究运用RT-PCR技术,首次从大熊猫(Ailuropoda melanoleuca)的肌肉组织总RNA中成功克隆了RPS24(Ribosomal Protein S24)基因的表达序列,并对其进行了测序及初步分析.结果表明:大熊猫RPS24基因的表达序列全长为431bp,开放阅读框(ORF)为399bp,编码132个氨基酸的蛋白质,该蛋白的分子量为15.3251kD,pI为10.92,含有7种类型共14个功能位点:即1个N-糖基化位点、2个cAMP和cGMP依赖性蛋白激酶磷酸化位点、6个蛋白激酶C磷酸化位点、1个酪蛋白激酶Ⅱ磷酸化位点、3个N-酰基化位点、1个酰胺化位点及1个RPS24e sig-nature.进一步分析发现,大熊猫RPS24基因与已报道的人、牛、苏门答腊猩猩、褐家鼠和小家鼠5个哺乳动物物种的表达序列及其编码的氨基酸序列具有很高的相似性:编码序列同源性分别为94.1%、92.4%、94.7%、89.9%和90.4%;与人RPS24蛋白的氨基酸序列同源性为98.48%,其余均为99.24%.展开更多
Metabolic reprogramming of host cells plays critical roles during viral infection.Itaconate,a metabolite produced from cis-aconitate in the tricarboxylic acid cycle(TCA)by immune responsive gene 1(IRG1),is involved in...Metabolic reprogramming of host cells plays critical roles during viral infection.Itaconate,a metabolite produced from cis-aconitate in the tricarboxylic acid cycle(TCA)by immune responsive gene 1(IRG1),is involved in regulating innate immune response and pathogen infection.However,its involvement in viral infection and underlying mechanisms remain incompletely understood.Here,we demonstrate that the IRG1-itaconate axis facilitates the infections of VSV and IAV in macrophages and epithelial cells via Rab GTPases redistribution.Mechanistically,itaconate promotes the retention of Rab GTPases on the membrane via directly alkylating Rab GDP dissociation inhibitor beta(GDI2),the latter of which extracts Rab GTPases from the membrane to the cytoplasm.Multiple alkylated residues by itaconate,including cysteines 203,335,and 414 on GDI2,were found to be important during viral infection.Additionally,this effect of itaconate needs an adequate distribution of Rab GTPases on the membrane,which relies on Rab geranylgeranyl transferase(GGTase-II)-mediated geranylgeranylation of Rab GTPases.The single-cell RNA sequencing data revealed high expression of IRG1 primarily in neutrophils during viral infection.Co-cultured and in vivo animal experiments demonstrated that itaconate produced by neutrophils plays a dominant role in promoting viral infection.Overall,our study reveals that neutrophils-derived itaconate facilitates viral infection via redistribution of Rab GTPases,suggesting potential targets for antiviral therapy.展开更多
文摘本研究运用RT-PCR技术,首次从大熊猫(Ailuropoda melanoleuca)的肌肉组织总RNA中成功克隆了RPS24(Ribosomal Protein S24)基因的表达序列,并对其进行了测序及初步分析.结果表明:大熊猫RPS24基因的表达序列全长为431bp,开放阅读框(ORF)为399bp,编码132个氨基酸的蛋白质,该蛋白的分子量为15.3251kD,pI为10.92,含有7种类型共14个功能位点:即1个N-糖基化位点、2个cAMP和cGMP依赖性蛋白激酶磷酸化位点、6个蛋白激酶C磷酸化位点、1个酪蛋白激酶Ⅱ磷酸化位点、3个N-酰基化位点、1个酰胺化位点及1个RPS24e sig-nature.进一步分析发现,大熊猫RPS24基因与已报道的人、牛、苏门答腊猩猩、褐家鼠和小家鼠5个哺乳动物物种的表达序列及其编码的氨基酸序列具有很高的相似性:编码序列同源性分别为94.1%、92.4%、94.7%、89.9%和90.4%;与人RPS24蛋白的氨基酸序列同源性为98.48%,其余均为99.24%.
文摘Metabolic reprogramming of host cells plays critical roles during viral infection.Itaconate,a metabolite produced from cis-aconitate in the tricarboxylic acid cycle(TCA)by immune responsive gene 1(IRG1),is involved in regulating innate immune response and pathogen infection.However,its involvement in viral infection and underlying mechanisms remain incompletely understood.Here,we demonstrate that the IRG1-itaconate axis facilitates the infections of VSV and IAV in macrophages and epithelial cells via Rab GTPases redistribution.Mechanistically,itaconate promotes the retention of Rab GTPases on the membrane via directly alkylating Rab GDP dissociation inhibitor beta(GDI2),the latter of which extracts Rab GTPases from the membrane to the cytoplasm.Multiple alkylated residues by itaconate,including cysteines 203,335,and 414 on GDI2,were found to be important during viral infection.Additionally,this effect of itaconate needs an adequate distribution of Rab GTPases on the membrane,which relies on Rab geranylgeranyl transferase(GGTase-II)-mediated geranylgeranylation of Rab GTPases.The single-cell RNA sequencing data revealed high expression of IRG1 primarily in neutrophils during viral infection.Co-cultured and in vivo animal experiments demonstrated that itaconate produced by neutrophils plays a dominant role in promoting viral infection.Overall,our study reveals that neutrophils-derived itaconate facilitates viral infection via redistribution of Rab GTPases,suggesting potential targets for antiviral therapy.
