Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nat Struct Mol Biol. 2011 Jan;18(1):94-9. doi: 10.1038/nsmb.1935. Epub 2010 Dec 12.
In the fission yeast S. pombe, the RNA interference (RNAi) pathway is required to generate small interfering RNAs (siRNAs) that mediate heterochromatic silencing of centromeric repeats. Here, we demonstrate that RNAi also functions to repress genomic elements other than constitutive heterochromatin. Using DNA adenine methyltransferase identification (DamID), we show that the RNAi proteins Dcr1 and Rdp1 physically associate with some euchromatic genes, noncoding RNA genes and retrotransposon long terminal repeats, and that this association is independent of the Clr4 histone methyltransferase. Physical association of RNAi with chromatin is sufficient to trigger a silencing response but not to assemble heterochromatin. The mode of silencing at the newly identified RNAi targets is consistent with a co-transcriptional gene silencing model, as proposed earlier, and functions with trace amounts of siRNAs. We anticipate that similar mechanisms could also be operational in other eukaryotes.
在裂殖酵母 S. pombe 中,RNA 干扰 (RNAi) 途径是产生小干扰 RNA (siRNA) 所必需的,这些 siRNA 介导着着丝粒重复序列的异染色质沉默。在这里,我们证明 RNAi 还可以抑制除组成型异染色质之外的基因组元件。我们利用 DNA 腺嘌呤甲基转移酶鉴定 (DamID) 技术,表明 RNAi 蛋白 Dcr1 和 Rdp1 与一些常染色质基因、非编码 RNA 基因和逆转录转座子长末端重复序列在物理上相互作用,并且这种相互作用不依赖于 Clr4 组蛋白甲基转移酶。RNAi 与染色质的物理结合足以引发沉默反应,但不足以组装异染色质。在新鉴定的 RNAi 靶标上的沉默模式与之前提出的共转录基因沉默模型一致,并且只需要痕量的 siRNA 即可发挥作用。我们预计类似的机制也可能在其他真核生物中起作用。