RNA干涉技术

RNAi是双链RNA介导的、序列特异性的转录后基因沉默，自1998年发现至今已有很大进展。本文综述了RNA干涉的分子机理及其应用研究进展。     

基因沉默及其生理学意义

基因沉默包括转录水平上的基因沉默和转录后水平上的基因沉默。发生沉默的基因可以是外源性转移基因,也可以是入侵的病毒或宿主内源性基因。双链RNA(dsRNA)作为启动因素或中间体为不同生物基因沉默所共有。基因沉默是生物体在基因调控水平上的一种自我保护机制。通过基因沉默,可以限制外来核酸的入侵;同时,基因沉默还与生物的生长发育有关。     

基于支持向量机的siRNA降解效率预测

为了辅助siRNA的设计,从已发表文献中共收集到573个siRNA的实验数据,使用基于统计学习理论的支持向量机(SVM)方法,提取了siRNA序列的碱基对关联性(BBC)特征,然后使用十倍交叉验证方法,对siRNA沉默目标基因的效率进行了预测.结果表明,基于支持向量机,选用多项式核作为核函数的算法具有最高的AUC值(0.73,ROC曲线图)和最高的r值(0.43,Pearson相关系数分析),优于以前基于打分的算法.结果说明,在以后的siRNA的设计中应该更多关注碱基之间的关联信息.     

miRNA:一种新的基因调控元件

miRNA(microRNA)是一类长约22个核苷酸的小分子非编码RNA。近年来,科学家发现miRNA与基因表达调控密切相关,miRNA可通过与靶mRNA特异性的碱基配对,引起靶mRNA的降解,抑制其翻译,或以其它形式的调节机制抑制靶基因的表达。本文概述了miRNA特点、生物合成过程、功能以及作用机制。     

认识小干扰RNA、微RNA和RNA干扰

近年来随着RNA干扰（RNAi）技术在生命领域的应用和小分子RNA研究的深入,RNA逐渐成为生命科学领域的一个研究热点。本文就RNA干扰技术及小干扰RNA（siRNA）和微RNA（m／RNA）间的关系进行了介绍。     

Silence of the genes

The 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig Mello for discovering “RNA interference—genesilencing by double-stranded RNA”. The Nobel Committee at the Karolinska Institute in Sweden selected them for the award for unraveling “a fundamental mechanism for controlling the flow of genetic information” that is “already being widely used in basic science as a method to study the function of genes and may lead to novel therapies in the future”. This has been one of the fastest Nobel Prizes conferred in physiology or medicine, considering that Fire and Mello published their path-breaking article in the journal Nature in 1998, less than ten years ago. Utpal Nath is an Assistant Professor in the Department of Microbiology and Cell Biology, IISc. His laboratory is studying the genetic mechanisms of plant development. Saumitra Das is an Associate Professor in the Department of Microbiology and Cell Biology, IISc. His laboratory is interested in the translational control of cellular and viral RNA.     

RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model

Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5×106 IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.     

RNA干扰及其应用综述

RNA干扰(RNA interference,RNAi)是真核生物中普遍存在的一种自然现象,是由双链RNA (double-stranded RNA,dsRNA)启动的序列特异的转录后基因沉默过程。在这一过程中,双链RNA被核酸内切酶切割成小干扰RNA(small interfering RNA,siRNA),小干扰RNA与相关的蛋白质结合成RNA 诱导沉默复合体(siRNA-induced silencing complex,RISC),RISC识别并降解靶mRNA。现在认为RNA 干扰是真核生物共有的抗病毒、抗转座子、抗转基因和抗异常RNA的基因组免疫系统。随着RNA干扰的研究,产生了一种新的技术——RNA干扰技术,并得到了广泛的应用。     

RNA干扰技术的研究进展

RNA组学研究日益蓬勃发展.RNA的相关研究被美国《科学》杂志评为2002年的十大进展.人们发现,双链RNA可以抑制含有特定序列的基因表达.应用这一特点,在生物体外强有力的使基因沉默,从而开创了一个新的和正在快速发展的生命科研领域.RNA干扰技术引起生物医学界几乎所有研究领域的广泛兴趣,它不仅揭示了细胞内基因沉默的机制,而且它还是基因功能分析的有力工具,RNA干扰(siRNA) 技术对人类有着巨大的意义和广阔的应用前景.     

RNA干扰技术和2006年诺贝尔医学奖

2006年诺贝尔医学奖授予两个美国科学家，表彰他们发现了RNA干扰现象即一种沉默基因和调控遗传信息流的重要机制。ＲＮＡi（RNA干扰）技术已成为研究基因功能的一种强有力的手段，并有望在未来帮助科学家研发出治疗疾病的新疗法。