Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Mol Cell. 2023 Nov 2;83(21):3835-3851.e7. doi: 10.1016/j.molcel.2023.09.033. Epub 2023 Oct 23.
PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.
PIWI 相互作用 RNA（piRNA）在动物生殖系中指导转座元件的沉默。在果蝇中，piRNA 由称为 piRNA 簇的异染色质位点产生，piRNA 簇作为关于基因组入侵物的信息库。双链簇的 piRNA 生成依赖于染色质结合的 Rhino-Deadlock-Cutoff（RDC）复合物，该复合物由 piRNA 指导的簇沉积，形成一个正反馈回路，其中 piRNA 促进其自身的生物发生。然而，在同源 piRNA 存在之前，piRNA 簇是如何形成的仍然未知。在这里，我们报告了从重复转基因序列自发产生的新的 piRNA 簇。簇的形成需要几个世代，并需要小 RNA 的连续跨代母本传递。我们发现，母源提供的小干扰 RNA（siRNA）触发了后代中新的簇激活。相比之下，在簇建立后，siRNA 对于簇功能是可有可无的。这些结果揭示了 siRNA 和 piRNA 途径之间意想不到的相互作用，并提出了 siRNA 触发新的 piRNA 簇形成的机制。
