Department of Biochemistry and Biophysics; University of California; San Francisco, CA USA.
RNA Biol. 2013 Nov;10(11):1653-60. doi: 10.4161/rna.26800.
The ability to distinguish self from non-self nucleic acids enables eukaryotes to suppress mobile elements and maintain genome integrity. In organisms from protist to human, this function is performed by RNA silencing pathways. There have been major advances in our understanding of the RNA silencing machinery, but the mechanisms by which these pathways distinguish self from non-self remain unclear. Recent studies in the yeast C. neoformans indicate that transposon-derived transcripts encode suboptimal introns and tend to stall in spliceosomes, which promotes the biogenesis of siRNA that targets these transcripts. These findings identify gene expression signal strength as a metric by which a foreign element can be distinguished from a host gene, and reveal a new function for introns and the spliceosome in genome defense. Anticipating that these principles may apply to RNA silencing in other systems, we discuss strong hints in the literature suggesting that the spliceosome may guide small RNA biogenesis in the siRNA and piRNA pathways of plants and animals.
真核生物能够区分自身和非自身的核酸，从而抑制移动元件并维持基因组完整性。在从原生生物到人类的生物体中，这一功能是由 RNA 沉默途径来执行的。我们对 RNA 沉默机制的理解已经取得了重大进展，但这些途径如何区分自身和非自身的机制仍不清楚。最近在酵母 C. neoformans 中的研究表明，转座子衍生的转录本编码次优内含子，并倾向于在剪接体中停滞，从而促进了针对这些转录本的 siRNA 的生物发生。这些发现确定了基因表达信号强度作为一种可以区分外源元件和宿主基因的度量，并揭示了内含子和剪接体在基因组防御中的新功能。预计这些原则可能适用于其他系统中的 RNA 沉默，我们讨论了文献中的有力暗示，表明剪接体可能在植物和动物的 siRNA 和 piRNA 途径中指导小 RNA 的生物发生。
