新近研究发现 ,人类 L a蛋白 (hum an L a protein,h L a)是一种与 HBV RNA转录调节相关的因子。L a蛋白可能结合在 HBV RNAs的茎环结构上 ,具有保护乙肝病毒 (hepatitis B virus,HBV) RNA,促进其翻译启动的作用 ,可能是 HBV RNA的稳定...新近研究发现 ,人类 L a蛋白 (hum an L a protein,h L a)是一种与 HBV RNA转录调节相关的因子。L a蛋白可能结合在 HBV RNAs的茎环结构上 ,具有保护乙肝病毒 (hepatitis B virus,HBV) RNA,促进其翻译启动的作用 ,可能是 HBV RNA的稳定因子。当 L a蛋白发生突变后将无法与 HBV RNA结合 ,丧失保护 HBV RNA的功能 ,使其受到酶的降解 ,无法转录翻译 ,病毒的复制受阻 ,从而抑制 HBV感染。本文综述了 L a蛋白、HBV RNA及核酶 (nuclear RNases)三者间相互作用关系的最新研究成果 ,从分子水平上探讨了导致 HBV RNA降解的可能机制 ,推测了野生型和突变型 L a蛋白对乙型肝炎病毒展开更多
The La (SS-B) autoimmune antigen is an RNA-binding protein that is present in both nucleus and cytoplasm of eukaryotic cells.The spectrum of RNAs that interact with the antigen includes species which also bind to the ...The La (SS-B) autoimmune antigen is an RNA-binding protein that is present in both nucleus and cytoplasm of eukaryotic cells.The spectrum of RNAs that interact with the antigen includes species which also bind to the interferon-inducible protein kinase PKR.We have investigated whether the La antigen can regulate the activity of PKR and have observed that both the autophosphorylation of the protein kinase that accompanies its activation by dsRNA and the dsRNA-dependent phosphorylation of the subunit of polypeptide chain initiation factor eIF-2 by PKR are inhibited in the presence of recombinant La antigen. This inhibition is partially relieved at higher concentrations of dsRNA.Once activated by dsRNA the protein kinase activity of PKR is insensitive to the La antigen. We have demonstrated by a filter binding assay that La is a dsRNA binding protein.Furthermore, when recombinant La is incubated with a 900bp synthetic dsRNA or with naturally occurring reovirus dsRNA it converts these substrates to single-stranded forms.We conclude that the La antigen inhibits the dsRNA-dependent activation of PKR by binding and unwinding dsRNA and that it may therefore play a role in the regulation of this protein kinase in interferon-treated or virus-infected cells.展开更多
Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries.Although effective vaccines for HAV are available,the deve...Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries.Although effective vaccines for HAV are available,the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists,such as Japan.There are two forms of antiviral agents against HAV:direct-acting antivirals (DAAs) and host-targeting agents (HTAs).Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection.Among the HTAs,amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication.Janus kinase (JAK) inhibitors inhibit La protein expression,HAV IRES activity,and HAV replication.Based on this review,both DAAs and HTAs may be needed to control effectively HAV infection,and their use should continue to be explored.展开更多
目的:分析微小核糖核酸-211(micro ribonucleic acid-211,miR-211)、La相关蛋白1(La-associated protein 1,LARP1)、转录辅助因子退变样蛋白4(transcription-assisted factor deformable protein 4,VGLL4)在胃癌组织中的表达及意义。方...目的:分析微小核糖核酸-211(micro ribonucleic acid-211,miR-211)、La相关蛋白1(La-associated protein 1,LARP1)、转录辅助因子退变样蛋白4(transcription-assisted factor deformable protein 4,VGLL4)在胃癌组织中的表达及意义。方法:收集98例胃癌患者,并取胃癌组织距离肿瘤边缘5 cm的癌旁组织43例。比较胃癌组织和癌旁组织miR-211,LARP1,VGLL4表达情况和以上指标与胃癌患者临床病理特征及生存情况的关系。结果:胃癌患者miR-211及LARP1高表达率高于癌旁组织,VGLL4高表达率低于癌旁组织(均P<0.05)。MiR-211,LARP1,VGLL4表达在TNM分期、淋巴结转移、浸润深度中差异有统计学意义(P<0.05)。MiR-211及LARP1高表达者3年生存率分别低于miR-211及LARP1低表达者,VGLL4高表达者3年生存率高于低表达者(P<0.05)。Cox比例风险模型分析显示TNM分期、淋巴结转移、浸润深度、miR-211、LARP1为胃癌预后的危险因素,VGLL4为保护因素。miR-211与LARP1呈正相关,miR-211与VGLL4,LARP1与VEGLL4呈负相关。结论:MiR-211及LARP1在胃癌组织中呈高表达,VGLL4呈低表达,和胃癌生物学行为相关,可能成为胃癌诊治的潜在生物学指标。展开更多
文摘The La (SS-B) autoimmune antigen is an RNA-binding protein that is present in both nucleus and cytoplasm of eukaryotic cells.The spectrum of RNAs that interact with the antigen includes species which also bind to the interferon-inducible protein kinase PKR.We have investigated whether the La antigen can regulate the activity of PKR and have observed that both the autophosphorylation of the protein kinase that accompanies its activation by dsRNA and the dsRNA-dependent phosphorylation of the subunit of polypeptide chain initiation factor eIF-2 by PKR are inhibited in the presence of recombinant La antigen. This inhibition is partially relieved at higher concentrations of dsRNA.Once activated by dsRNA the protein kinase activity of PKR is insensitive to the La antigen. We have demonstrated by a filter binding assay that La is a dsRNA binding protein.Furthermore, when recombinant La is incubated with a 900bp synthetic dsRNA or with naturally occurring reovirus dsRNA it converts these substrates to single-stranded forms.We conclude that the La antigen inhibits the dsRNA-dependent activation of PKR by binding and unwinding dsRNA and that it may therefore play a role in the regulation of this protein kinase in interferon-treated or virus-infected cells.
文摘Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries.Although effective vaccines for HAV are available,the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists,such as Japan.There are two forms of antiviral agents against HAV:direct-acting antivirals (DAAs) and host-targeting agents (HTAs).Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection.Among the HTAs,amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication.Janus kinase (JAK) inhibitors inhibit La protein expression,HAV IRES activity,and HAV replication.Based on this review,both DAAs and HTAs may be needed to control effectively HAV infection,and their use should continue to be explored.
文摘目的:分析微小核糖核酸-211(micro ribonucleic acid-211,miR-211)、La相关蛋白1(La-associated protein 1,LARP1)、转录辅助因子退变样蛋白4(transcription-assisted factor deformable protein 4,VGLL4)在胃癌组织中的表达及意义。方法:收集98例胃癌患者,并取胃癌组织距离肿瘤边缘5 cm的癌旁组织43例。比较胃癌组织和癌旁组织miR-211,LARP1,VGLL4表达情况和以上指标与胃癌患者临床病理特征及生存情况的关系。结果:胃癌患者miR-211及LARP1高表达率高于癌旁组织,VGLL4高表达率低于癌旁组织(均P<0.05)。MiR-211,LARP1,VGLL4表达在TNM分期、淋巴结转移、浸润深度中差异有统计学意义(P<0.05)。MiR-211及LARP1高表达者3年生存率分别低于miR-211及LARP1低表达者,VGLL4高表达者3年生存率高于低表达者(P<0.05)。Cox比例风险模型分析显示TNM分期、淋巴结转移、浸润深度、miR-211、LARP1为胃癌预后的危险因素,VGLL4为保护因素。miR-211与LARP1呈正相关,miR-211与VGLL4,LARP1与VEGLL4呈负相关。结论:MiR-211及LARP1在胃癌组织中呈高表达,VGLL4呈低表达,和胃癌生物学行为相关,可能成为胃癌诊治的潜在生物学指标。
