Cells in the ovary of a fly expressing two proteins, shown in red and green, that work together to silence harmful transposable elements within the genome. Image credit: Marzia Munafò (CC BY 4.0)
For an organism to form and grow correctly, it must rely on the genetic information it has received from its parents. DNA, however, is full of elements called transposons that can disrupt this information by moving around the genome and inserting themselves into genes. Changes caused by these invading elements can lead to devastating effects, such as cancer and cell death. To shield their DNA from harm, organisms have evolved regulatory machineries to recognize and correct alterations that may be damaging.
One way cells can protect their DNA is by silencing disruptive transposons using small molecules known as piRNAs. These protective molecules detect transposons as soon as they are active and recruit other proteins to switch them off. However, questions still remain about how specific proteins recruited by piRNAs are involved in this process. In flies, a protein called Panoramix (Panx) is known to trigger transposon silencing, but how it does this is still unclear.
Now, Fabry, Ciabrelli, Munafò et al. set out to investigate how Panx silences active transposons in the ovaries of flies and whether other proteins are involved. Like so many other proteins, Panx was found not to work alone but to form a complex with two other proteins, called Nxf2 and Nxt1. The experiments showed that all three components of the complex, named PICTS, are critical for transposon control in flies, but Panx is the engine that drives the machine.
Panx and Nxf2 were found to stabilize each other, and together with co-factor Nxt1 place a mark on the genome at the point where the transposon emerges, effectively switching it off. Notably, although Nxf2 and Nxt1 are part of a family of proteins that export molecules from the nucleus, both these factors appear to have been repurposed to silence transposable elements within the genome.
This work expands our understanding of how cells employ regulatory machineries, like the PICTS complex, to guard against disruptive genetic changes. These mechanisms are often conserved throughout evolution, and the findings presented here may help identify ways to counteract harmful changes caused by transposons in other organisms, including humans. However, more work would be required to deepen our knowledge of how these processes work.
