Studies have found that multiple generations of cytoplasmic RNA interference play an important role

Copyright © iCell Bioscience Inc, Shanghai 2018-2019

Multiple generations of RNA interference have been an important research area. In 2012, Prof. Craig Mello, Prof. Scott Kennedy and Prof. Eric Miska published three articles on Nature and Cell respectively, reporting key proteins in the nuclear RNA interference pathway (Nrde), especially the Argonaute protein HRDE- 1, plays an important role in multiple generations of RNA interference.

Recently, Professor Craig Mello, Prof. Scott Kennedy, and Guang Shouhong's research group published three articles on Mol Cell, Nature, and Cell Reports at the same time, pointing out that the cytoplasmic RNA interference machinery also plays an important role in multiple generations of RNA interference.

The Ginseng Red Research Group has discovered a new cytoplasmic Argonaute protein, WAGO-4, involved in multiple generations of RNA interference. WAGO-4 localizes to the germinal cells in close proximity to the nucleus of the membrane-free organelles and presents an asymmetric distribution during early embryonic development. WAGO-4 binds heritable small RNAs across generations and specifically targets mRNA, down-regulating the expression of target mRNAs. The WAGO-4 bound endogenous small RNA can be uracil modified at the 3' The uracil transferase CDE-1 may promote the genetic process of RNA interference by modifying the WAGO-4 bound small RNA.

Finally, WAGO-4 may be involved in the transfer of small RNAs from parent to offspring. The Scott Kennedy group found that ZNFX-1 and WAGO-4 are located in a new droplet organelle - Z granules. WAGO-4/ZNFX-1 co-promote the maintenance of small RNA expression in offspring. Through more detailed observations, Z-granules and previous organelles P-granules and Mutator foci have formed multiple droplet organelles.

Such an orderly droplet of time and space can help cells perform fine RNA regulation. The Craig Mello group found that ZNFX-1 protein directly binds to RdRP protein and some Argonaute proteins through immunoprecipitation. At the same time, ZNFX-1 is crucial for the production of small RNA near the piRNA site, which promotes the balance of amplification of small RNAs.