Gene silencing：Double－stranded RNA mediated mRNA degradation and gene inactivation

INTRODUCTIONThe genome structure of plants can be alteredby genetic transformation. During the process ofgene transfer, Agrobacterium tumefaCJens integratepart of their genome into the genome of susceptiblespecies. Recently, genetic transfOrmation techniqueshave been used to modify significantly the organi-zation of the genome. Introducing transgenes intop1ants can both modify the number of copies of agiven sequence and affect gene expression. Becausethe expression of a transgene cannot…     

Micro RNA and viral infections in mammals

RNA silencing plays an important role in development through the action of micro (mi) RNAs that fine tune the expression of a large portion of the genome. But, in plants and insects, it is also a very important player in innate immune responses, especially in antiviral defense. It is now well established that the RNA silencing machinery targets plant as well as insect viruses. While the genetic basis underlying this defense mechanism in these organisms starts being elucidated, much less is known about the possible antiviral role of RNA silencing in mammals. In order to identify siRNAs coming from viruses in infected human cells, small RNAs from cells infected with RNA viruses, such as hepatitis C virus, yellow fever virus or HIV-1, were cloned and sequenced, but no virus-specific siRNAs could be detected. On the contrary, viral small RNAs were found in cells infected by the DNA virus Epstein-Barr. A closer look at these revealed that they were not siRNAs, but rather resembled miRNAs. This finding indicated that, rather than being targeted by RNA silencing, human DNA viruses seem to have evolved their own miRNAs to modulate the expression of host genes. This primary observation has been extended to other members of the herpesvirus family as well as other DNA viruses such as the polyomavirus SV40. Viral miRNAs have the potential to act both in cis to regulate expression of viral genes, or in trans on host genes. There are good indications for the cis mode of action, but the identification of cellular targets of these small viral regulators is only in its infancy.     

microRNA的调控和被调控

microRNA是一大类长度约22 nt的非编码RNA,可与靶基因的3′-UTR区部分或完全配对结合,进而通过降低靶mRNA的稳定性或抑制翻译而下调目的基因的表达. microRNA不仅参与细胞的增殖、分化、死亡等正常生理过程,而且还与包括癌症在内的诸多病理过程密切相关.microRNA通常位于编码基因的内含子区,主要由RNA聚合酶Ⅱ催化而转录为初始microRNA,接着经过一系列的核内、胞浆内酶切步骤而组装成有功能的RNA诱导的沉默复合体.本文将在简要介绍microRNA生物合成和调控功能的基础上,重点综述microRNA被调控的研究进展,主要包括表观遗传学水平、转录水平、转录后水平和降解的调控.近年来的研究,逐步丰富甚至推翻了以往对microRNA的认识,体现了microRNA生物学的复杂性.可以预见,随着研究的深入,microRNA将在疾病的早期防治中发挥越来越重要的作用.     

双链RNA在基因沉默中的作用

介绍依赖于同源识别的基因沉默 .依赖于同源识别的基因沉默 ,是指向生物体内导入外源核酸时引起相应序列的内源基因的表达被特异性抑制的一种基因调控现象 .基因沉默分为转录基因沉默和转录后基因沉默 ,二者都通过双链RNA介导 .它们是真核生物中普遍存在的抵抗病毒入侵、抑制转座子活动、调控基因表达的监控机制 .这些机制具有巨大的应用前景 .