转录水平siRNA介导的基因沉默

Gene Silence by siRNA at Transcriptional Level

siRNA(smallinterferenceRNA)在转录后水平有效地沉默基因表达的现象称为RNAi(RNAinterference,RNA干涉),传统认为它能在转录后水平上有效地沉默基因的表达(posttranscriptionalgenesilence,PTGS)。然而,最近实验研究表明,siRNA是一些甲基化转移酶活化的起始信号,在siRNA的作用下,甲基化转移酶使DNA区域包括胞嘧啶鸟嘌呤核苷酸连续区(称为CG岛),CNG(N:A/T/C/G),CHH(H:A/C/T)中的胞嘧啶核苷C和组蛋白H3亚基第9个赖氨酸K(lysineresidueK9inhistoneH3,H3K9)发生甲基化,基因表达为此而受到抑制,即siRNA能在转录水平调控基因的表达(transcriptionalgenesilence,TGS).同时,siRNA在异染色质的形成中也起着重要的作用,RNAi突变会激活原异染色质区域中沉默基因的表达。

siRNA （small interference RNA ） silences a gene expression effectively at post-transcriptional level （PTGS）, which is called RNAi （RNA interference） traditionally. However, recent studies reveal that siRNAs initiate the activation of Methytransferases, which cause the methylation of the DNA at the sites of CG, CNG （N： A/T/C/G）, CHH （H： A/C/T） in which the cytosine （C） is methylated and cause the methylation of the histone at lysine residue K9 in histone H3, so the gene expression is inhibited because of the mentylation. This phenomenon indicates that siRNAs not only silence gene expression at post-transcriptional level but also at transcriptional level through the methylation of DNA and histone. Meanwhile, siRNAs are also involved in the formation of heterochromatin. Mutation of RNAi will activate a gene lying at heterochromatic loci in which the gene was silenced, in other words, RNAi causes the formation of heterochromatin and genes silence in it.