microRNA与免疫调控

微小RNA(microRNA)又简称miRNA,是一类长约21～25个核苷酸的小分子RNA,能与特定的信使RNA靶向结合,在转录后水平调控基因表达.越来越多的证据表明,miRNA可通过靶向免疫系统中关键信号转导分子的表达,从而在多个环节上参与调控机体固有免疫反应和适应性免疫反应.已经发现,miRNA参与调节肿瘤、类风湿...     

miRNA与固有免疫

固有免疫是宿主防御病原体入侵的第一道防线, microRNA （ miRNA）是能够调节基因mRNA表达的一组非蛋白编码小RNA分子,其表达具有空间和时间上的特异性,是调控其它功能基因表达的重要分子。 miRNA参与固有免疫应答,并对其发挥重要的调控作用。文章从miRNA对固有免疫受体信号通路和固有免疫细胞的调节两方面阐述了miRNA对固有免疫的调节作用。     

lncRNA与miRNA相互作用对疾病的影响

长链非编码RNA(lncRNA)与微小RNA(miRNA)之间存在相互调控关系。lncRNA可作为一种竞争性内源性RNA(ceRNA)与miRNA相互作用,参与靶基因的表达调控,反之,miRNA可通过RNA诱导沉默复合物(RISC)调控lncRNA发挥生物学功能,两者共同参与多种疾病的发生。     

微小RNA在肿瘤侵袭转移中的作用

微小RNA(miRNA)是一类长度为19-25个核苷酸对的非编码小分子RNA,通过与靶 mRNA互补配对而在转录水平上对基因的表达进行负调控.实验表明miRNA可通过调控其靶基因参与的信号通路,影响肿瘤的发生、发展和转移,发挥着类似原癌基因或抑癌基因的功能.因此研究miRNA在肿瘤侵袭转移调控中的作用有着重要意义.     

小RNA与阿尔茨海默病发病机制研究进展

小RNA(miRNA)是一类非编码的小RNA,通过转录后水平调控细胞蛋白质的表达,在神经系统的生长发育、分化及功能执行中发挥重要的作用.脑组织内miRNA的异常表达可通过多种途径影响阿尔茨海默病的发生和发展.对于miRNA的研究将有助于深入了解阿尔茨海默病的发病机制.     

miRNA和转录因子SOX家族的关系研究

小分子RNA(miRNA)是一类在转录后水平调控基因表达的小分子非编码RNA,转录因子SOX家族可参与调节多种生理病理过程.目前关于二者间的调控关系已有一些报道,本文对此领域的进展进行大致总结,以期为进一步完善分子调控网络提供参考资料.     

MicroRNA在类风湿关节炎中的作用

MicroRNA(miRNA)是一类新型保守的非编码单链小分子RNA,能够在转录后水平调节mRNA表达导致蛋白翻译抑制或促进靶mRNA降解.到目前为止,在生物界已发现5000多种miRNA,在miRBase所登记的miRNA数据库中仅人类就有千余种,预计人类有超过30％的蛋白编码基因受miRNA调控.免疫细胞中表达多种miRNA,对固有免疫和适应性免疫的分子通路和细胞分化及功能有广泛的影响,其表达失调将导致免疫相关的疾病(如类风湿关节炎),因此研究miRNA对诊断各种疾病类型及预后有潜在临床应用价值.     

miRNA与固有免疫

miRNA是近年来发现的一种小分子RNA,参与细胞分化、生长发育等多种生物学过程,与人类疾病密切相关。最近,有研究发现miRNA可以通过TLR的信号转导途径和细胞因子反应参与固有免疫。本文对miRNA和RNA干扰在固有免疫反应中的调控作用作一综述。     

microRNA与肿瘤发生的关系及在临床诊治中应用

microRNA(miRNA)是一类内源性非编码小分子RNA,通过阻遏mRNA的翻译来调控基因的表达,大量研究证明其与肿瘤的发生密切相关.该文将重点论述调控肿瘤发生、发展的miRNA,详细阐述这些短片段RNA在肿瘤的分子诊断及临床个体性治疗中的应用.     

miRNA与肿瘤

microRNA又称miRNA，是真核生物细胞中固有的一类长度约为22个核苷酸且不编码蛋白的小分子RNA。miRNAs广泛参与动植物生命活动的调控，如生长发育、营养物质的代谢和激素的分泌等。近年的研究表明miRNA通过调控细胞增殖、凋亡和分化在肿瘤的发生和发展中起着重要的作用。研究miRNA与肿瘤的关系将为肿瘤的诊断和治疗提供新的思路。     

HIV-l and the microRNA-guided silencing pathway: an intricate and multifaceted encounter

MicroRNAs (miRNAs) are approximately 21-24 nucleotide RNAs that mediate repression of messenger RNA (mRNA) translation through recognition of specific miRNA binding sites usually located in the 3' non-translated region. Designed to simulate miRNAs, small interfering RNAs represent a powerful genetic approach to potently inhibit gene expression by mediating cleavage of the intended mRNA target. This strategy has been applied successfully to suppress replication of several viruses, including human immunodeficiency virus type 1 (HIV-1). However, recent evidences indicate that viral RNAs may themselves be processed, to some extent, by the endogenous miRNA biosynthetic machinery in mammalian cells, extending previous observations in plants. The resulting viral miRNAs may exert regulatory effects towards host and/or viral genes that may influence viral replication and modulate the course of infection. Viral miRNA generation and/or action may be limited by counteraction through inhibitory viral RNAs and/or proteins. This review article will focus on the relationship between HIV-1 and miRNA-guided RNA silencing, and discuss the different aspects of their interaction. As we learn more about the mechanism and importance of small RNA-based antiviral systems, a more intricate picture of the interaction between HIV-1 and a proven antiviral defense mechanism in lower eukaryotes is emerging.     

Roles of host and viral microRNAs in human cytomegalovirus biology

Human cytomegalovirus (HCMV) has a relatively large and complex genome, a protracted lytic replication cycle, and employs a strategy of replicational latency as part of its lifelong persistence in the infected host. An important form of gene regulation in plants and animals revolves around a type of small RNA known as microRNA (miRNA). miRNAs can serve as major regulators of key developmental pathways, as well as provide subtle forms of regulatory control. The human genome encodes over 900 miRNAs, and miRNAs are also encoded by some viruses, including HCMV, which encodes at least 14 miRNAs. Some of the HCMV miRNAs are known to target both viral and cellular genes, including important immunomodulators. In addition to expressing their own miRNAs, infections with some viruses, including HCMV, can result in changes in the expression of cellular miRNAs that benefit virus replication. In this review, we summarize the connections between miRNAs and HCMV biology. We describe the nature of miRNA genes, miRNA biogenesis and modes of action, methods for studying miRNAs, HCMV-encoded miRNAs, effects of HCMV infection on cellular miRNA expression, roles of miRNAs in HCMV biology, and possible HCMV-related diagnostic and therapeutic applications of miRNAs.     

Not miR-ly small RNAs: big potential for microRNAs in therapy

RNA interference (RNAi) describes a set of natural processes in which genes are silenced by small RNAs. RNAi has been widely used as an experimental tool that has recently become the focus of drug development efforts to treat a variety of diseases and disorders. Like all molecular therapies, in vivo delivery is the major hurdle to realizing therapeutic RNAi. Several strategies have been developed that increase small RNA half-life in the blood, facilitate transduction across biological membranes, and mediate cell-specific delivery. Importantly, these strategies permit targeting of mRNAs as well as microRNAs (miRNAs), a class of small RNAs encoded in the genome. miRNAs are required for multiple developmental and cellular processes. Dysfunction of miRNAs can result in a host of pathologies, suggesting that miRNAs are potential targets of therapy. Recent studies of miRNA function in immune-specific pathways indicate that specific miRNAs might be exploited as therapeutic targets to treat immune disorders, including autoimmunity, allergy, and hematopoietic cancers.     

基因组编辑技术在病毒相关恶性疾病中的应用

某些病毒感染人类引起相应的疾病,病毒首先通过细胞表面的受体侵入细胞内,然后利用宿主复制系统进行病毒基因组的复制、转录、翻译等完成其生活周期,组装成完整病毒,某些病毒基因组会整合到宿主基因组引起宿主细胞的过度增殖而引起恶性疾病.基因组编辑技术通过靶向病毒基因组,清除宿主细胞内游离或整合的病毒从根本上治愈疾病.主要从三大基因组编辑技术的作用机制以及在病毒相关疾病中的应用等方面进行阐述.     

Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

Analysis of virus-host interactions has revealed a variety of ways in which viruses utilize and/or alter host functions in an effort to facilitate efficient replication. Recent work has suggested that certain RNA viruses that replicate in the cytoplasm disrupt the normal trafficking of cellular RNAs and proteins within the host cell. This review will examine the recent evidence showing that poliovirus and vesicular stomatitis virus (VSV) can inhibit nucleo-cytoplasmic transport within cells. Interestingly, the data indicate that inhibition by both viruses involves targeting components of the nuclear pore complex (NPC). Following this, several possible explanations for why viruses might disrupt nucleo-cytoplasmic transport are discussed. Finally, the possibility that disruption of nucleo-cytoplasmic trafficking may be a more common feature of RNA virus-host interactions than previously thought is examined.     

Does RNA interference have a future as a treatment for HIV-1 induced disease?

RNA interference has recently emerged as an effective way to block the expression of specific messenger RNAs in eukaryotic cells. Using this approach, it has proven possible to block the replication of HIV-1 in cultured cells using small interfering RNAs targeted to viral sequences or to host messenger RNAs that encode factors critical for virus replication, such as the CCR-5 coreceptor. Unfortunately, the high sequence specificity of RNA interference, combined with the known tendency of HIV-1 to rapidly generate sequence variability, means that HIV-1 variants resistant to individual small interfering RNAs targeted to the viral genome arise rapidly. However, this problem may be circumvented by simultaneously targeting several essential HIV-1 sequences using RNA interference, or by targeting host genes that are essential for virus replication. Thus, RNA interference-based approaches have the potential to prove useful as novel treatments for HIV-1 induced disease, although the problem of how to efficiently deliver small interfering RNA expression vectors, or the small interfering RNAs themselves, to cells susceptible to HIV-1 infection in vivo, remains to be resolved.     

Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression

Dicer is essential for plant, Caenorhabditis elegans, and Drosophila antiviral responses because of its role in generating small interfering RNA (siRNA) from viral genomes. We show that because of impaired miRNA production, mice with a variant Dicer1 allele (Dicer1(d/d)) were more susceptible to vesicular stomatitis virus (VSV) infection. We did not detect VSV genome-derived siRNA in wild-type cells or any alteration of interferon-mediated antiviral responses by Dicer1 deficiency. Rather, we found that host miR24 and miR93 could target viral large protein (L protein) and phosphoprotein (P protein) genes, and a lack of miR24 and miR93 was responsible for increased VSV replication in Dicer1(d/d) cells. Our data suggest that host miRNA can play a role in host interactions with viruses.