2′-5′-Oligoadenylate synthetase like protein(OASL) plays a key role in response to viral infections through selectively activating the OAS/RNase L or OASL/RIG-I signaling pathway.Although classic pathway of OASL is ...2′-5′-Oligoadenylate synthetase like protein(OASL) plays a key role in response to viral infections through selectively activating the OAS/RNase L or OASL/RIG-I signaling pathway.Although classic pathway of OASL is well-known,its regulated genes or co-actors are largely unknown.To study the possible molecular mechanism of duck OASL(dOASL),we performed RNA-sequencing(RNA-seq) and immunoprecipitation and mass spectrometry(IP-MS) at the level of mRNA and protein,respectively.For RNA-seq,we used DF1 cell lines(DF1 dO ASL+/+,DF1 cO ASL–/–,and DF1) with or without the CK/0513 H5 N1 virus(A/chicken/huabei/0513/2007) infection.1 737 differentially expressed genes(DEGs) were identified as candidate target genes regulated by dOASL.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis and Weighted Correlation Network Analysis(WGCNA) were performed.We identified one important yellow co-expression module correlated with antiviral immune response.In this module,Ankyrin repeat and FYVE domain containing 1(ANKFY1),harboring a BTB domain similar to the methyl CpG-binding protein 1(MBD1) which bound to OASL in human,was regulated by dOASL.At protein level,133 host proteins were detected.Interestingly,ANKFY1 was one of them binding to dOASL protein.Further phylogenomic and chromosomal syntenic analysis demonstrated MBD1 was absent in birds,while mammals retained.It is suggested that OASL-ANKFY1 interaction might act as a compensatory mechanism to regulate gene expression in birds.Our findings will provide a useful resource for the molecular mechanism research of dOASL.展开更多
寡腺苷酸合成酶（Oligoadenylate synthetase,OAS）家族蛋白是典型的抗病毒蛋白,其家族成员寡腺苷酸合成酶1~3（OAS1~3）和寡腺苷酸合成酶样蛋白（Oligonucleotide synthase-like protein synthetase,OASL）在抗病毒天然免疫应答中发挥...寡腺苷酸合成酶（Oligoadenylate synthetase,OAS）家族蛋白是典型的抗病毒蛋白,其家族成员寡腺苷酸合成酶1~3（OAS1~3）和寡腺苷酸合成酶样蛋白（Oligonucleotide synthase-like protein synthetase,OASL）在抗病毒天然免疫应答中发挥着重要作用。病毒感染机体后,细胞分泌的干扰素（Interferon,IFN）会诱导寡腺苷酸合成酶家族蛋白合成,其可通过核糖核酸酶L（RNase L）依赖途径和非依赖途径发挥抗病毒作用。本综述主要讨论寡腺苷酸合成酶家族蛋白的抗病毒机制与抗病毒临床应用的相关研究进展。展开更多
Mycobacterium tuberculosis(M.tuberculosis)can replicate in the macrophage by interfering with many host protein functions.While it is far from known these host proteins for controlling M.tuberculosis infection.Herein,...Mycobacterium tuberculosis(M.tuberculosis)can replicate in the macrophage by interfering with many host protein functions.While it is far from known these host proteins for controlling M.tuberculosis infection.Herein,we infected macrophages including THP-1 and Raw264.7 cells with M.tuberculosis and identified the differentially expressed genes(DEGs)in the interferon signaling pathway.Among them,2'-5'oligoadenylate synthetase-like(OASL)underwent the greatest upregulation in M.tuberculosis-infected macrophages.Knockdown of the expression of OASL attenuated M.tuberculosis survival in macrophages.Further,bioinformatics analysis revealed the potential interaction axis of OASL-TAB3-RvO127,which was further validated by the yeast-two-hybrid(Y2H)assay and Co-IP.This interaction axis might regulate the M.tuberculosis survival and proliferation in macrophages.The study reveals a possible role of OASL during M.tuberculosis infection as a target to control its propagation.展开更多
基金the National Natural Science Foundation of China(31772587)the National Key Research and Development Program of China(2016YFD0500202)
文摘2′-5′-Oligoadenylate synthetase like protein(OASL) plays a key role in response to viral infections through selectively activating the OAS/RNase L or OASL/RIG-I signaling pathway.Although classic pathway of OASL is well-known,its regulated genes or co-actors are largely unknown.To study the possible molecular mechanism of duck OASL(dOASL),we performed RNA-sequencing(RNA-seq) and immunoprecipitation and mass spectrometry(IP-MS) at the level of mRNA and protein,respectively.For RNA-seq,we used DF1 cell lines(DF1 dO ASL+/+,DF1 cO ASL–/–,and DF1) with or without the CK/0513 H5 N1 virus(A/chicken/huabei/0513/2007) infection.1 737 differentially expressed genes(DEGs) were identified as candidate target genes regulated by dOASL.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis and Weighted Correlation Network Analysis(WGCNA) were performed.We identified one important yellow co-expression module correlated with antiviral immune response.In this module,Ankyrin repeat and FYVE domain containing 1(ANKFY1),harboring a BTB domain similar to the methyl CpG-binding protein 1(MBD1) which bound to OASL in human,was regulated by dOASL.At protein level,133 host proteins were detected.Interestingly,ANKFY1 was one of them binding to dOASL protein.Further phylogenomic and chromosomal syntenic analysis demonstrated MBD1 was absent in birds,while mammals retained.It is suggested that OASL-ANKFY1 interaction might act as a compensatory mechanism to regulate gene expression in birds.Our findings will provide a useful resource for the molecular mechanism research of dOASL.
基金funded by the National Natural Science Foundation of China(Grant No.31602061,U21A20259,31872470)the National Key Research and Development Program of China(Grant No.2021YFD1800401).
文摘Mycobacterium tuberculosis(M.tuberculosis)can replicate in the macrophage by interfering with many host protein functions.While it is far from known these host proteins for controlling M.tuberculosis infection.Herein,we infected macrophages including THP-1 and Raw264.7 cells with M.tuberculosis and identified the differentially expressed genes(DEGs)in the interferon signaling pathway.Among them,2'-5'oligoadenylate synthetase-like(OASL)underwent the greatest upregulation in M.tuberculosis-infected macrophages.Knockdown of the expression of OASL attenuated M.tuberculosis survival in macrophages.Further,bioinformatics analysis revealed the potential interaction axis of OASL-TAB3-RvO127,which was further validated by the yeast-two-hybrid(Y2H)assay and Co-IP.This interaction axis might regulate the M.tuberculosis survival and proliferation in macrophages.The study reveals a possible role of OASL during M.tuberculosis infection as a target to control its propagation.
