Drosophila animal experiment reveals the occurrence and regulation mechanism of small molecule piRNAs

  Small piRNA (RNA that interacts with Piwi) plays an important role in inhibiting transposon activity and maintaining genome stability, but the molecular mechanism (molecular mechanism) of its development and regulation is still unknown. Drosophila germ cells provide an excellent model for studying this mechanism. The development of piRNA in Drosophila germ cells involves two processes, primary and secondary. The piRNA secondary processing pathway (also known as the "ping-pong" cycle) is regulated by PIWI family proteins (AGO3 and AUB). This effect leads to a significant expansion of piRNA in the cell. Existing hypotheses indicate that, in the ping-pong cycle, PIWI family members AUB and AGO3 perform targeted cleavage through the target RNA recognized by piRNA, resulting in piRNA amplification in the second cycle. I'm.

  However, whether and how the AGO3 slicer activity works has always been an important scientific problem to be solved in this field. A study by Chen Dahua's laboratory at the Institute of Zoology, Chinese Academy of Sciences found that the activity of the AGO3 slicer is essential for the secondary amplification of piRNA. AGO3 suppresses the AUB:AUB ping-pong cycle in a way that has nothing to do with the activity of the slicer. They further studied and found that the slice mutant of AGO3 caused the ectopic expression of Armitage, the main processing protein of piRNA. As a key member of the primary processing pathway of piRNA, Armitage protein usually appears in the cytoplasm and mitochondria, while the AGO3 slicer mutant causes Armitage protein to appear in the organelles at the secondary processing site of piRNAs. Importantly, this study found that AGO3 interacts with ordnance and is also present in mitochondria. In addition, AGO3 also interacts with another mitochondrial protein, zucchini, and regulates the dynamic shuttle of the AGO3/Armitage complex between mitochondria and nuclear fusion, thereby participating in the assembly of the AGO3ISC complex in nuclear fusion. I will. This study puts forward the view that mitochondria and nuage coordinate the secondary processing of piRNA, and provides a theoretical basis for further understanding of the development mechanism of piRNA.