Mechanism of RNAi
RNAi is activated by the presence of long, perfect or imperfect dsRNAs that are recognized and specifically cleaved by an Rnase III enzyme called Dicer or Dicer-like (DCL), to give small dsRNAs of 21–26 nucleotides. These small dsRNAs are then recognized, unwound and incorporated as single stranded RNAs into a protein complex known as RISC (RNA-induced silencing complex), where they serve to direct, through sequence complementarity, the cleavage or the translational repression of target mRNAs by proteins of the Argonaute family.
First, miRNAs derive from genomic loci distinct from other recognized genes, whereas siRNAs often derive from mRNAs, transposons, viruses, or heterochromatic DNA.
Second, miRNAs are processed from transcripts that can form local RNA hairpin structures, whereas siRNAs are processed from long bimolecular RNA duplexes or extended hairpins.
Third, a single miRNA:miRNA* duplex is generated from each miRNA hairpin precursor molecule, whereas a multitude of siRNA duplexes are generated from each siRNA precursor molecule, leading to many different siRNAs accumulating from both strands of this extended dsRNA.
Fourth, miRNA sequences are nearly always conserved in related organisms, whereas endogenous siRNA sequences are rarely conserved.
Fifth, concerning the biological targets of miRNAs and endogenous siRNAs, endogenous siRNAs typically specify “auto-silencing,” in that they specify the silencing of the same locus (or very similar loci) from which they originate, whereas miRNAs specify “hetero-silencing,” in that they are produced from genes that specify the silencing of very different genes.
參考答案:RNA干扰机理
RNA干扰是由长链型、完全型或不完全型双链RNA激活的，这些双链RNA被识别并被一种叫做“Dicer”（切割器）或者“DCL” (切割器形) 的RNA酶III进行特异性剪切，得到21–26个核苷酸的小型双链。然后这些小型双链RNA以单链RNA的形式被识别、解链和重组为RISC (RNA诱导沉默蛋白复合体)，在此他们直接由Argonaute 家族的蛋白质通过序列互补、剪切或翻译表达为靶标信使RNA。
第一，微小RNA 起源于明显不同于其他识别基因的基因位点，而小型干扰RNA通常起源于信使RNA、转座子、病毒 或异染色质的 DNA。
第二，微小RNA由能形成局部RNA 发夹结构的转录体加工而成，而小型干扰RNA 由长链双分子RNA双链体或拓展发夹结构加工而成。
再次， 单个“微小RNA：微小RNA”双链体起源于每个微小RNA发夹结构的前体分子, 而小型干扰RNA 双链体集合体起源于每个小型干扰RNA前体分子，导致了许多不同的小型干扰RNA在这种拓展型的双链RNA的双链上聚合。
第四，相关生物中的微小RNA序列几乎总是保守的，而外源小型干扰RNA 序列很少是保守。
第五，关于微小RNA 和外源小型干扰RNA的生物靶标方面，外源小型干扰RNA是典型的 “自动沉默”，也就是它们在其起源的同一位点(或非常相似的位点)沉默，而微小RNA 是“异位沉默”，也就是它们是由具备非常不同的沉默的基因产生的。
重点词汇掌握：
RNA ：脱氧核糖核酸
RNAi全称：RNA interference，翻译成“RNA干扰”
dsRNAs全称：Double-stranded RNAs，翻译成“双链RNA”
miRNA：微小RNA
siRNA：小型干扰RNA
