The moonlighting gatekeeper
In fruit flies, proteins that control molecular traffic also help to silence parasitic genetic elements.
Transposons are genetic sequences, which, when active, can move around the genome and insert themselves into new locations. This can potentially disrupt the information required for cells to work properly: in reproductive organs, for example, transposon activity can lead to infertility. Many organisms therefore have cellular systems that keep transposons in check.
Animal cells comprise two main compartments: the nucleus, which contains the genetic information, and the cytosol, where most chemical reactions necessary for life take place. Molecules continually move between nucleus and cytosol, much as people go in and out of a busy train station. The connecting ‘doors’ between the two compartments are called Nuclear Pore Complexes (NPCs), and their job is to ensure that each molecule passing through reaches its correct destination.
Recent research shows that the individual proteins making up NPCs (called nucleoporins) may play other roles within the cell. In particular, genetic studies in fruit flies suggested that some nucleoporins help to control transposon activity within the ovary – but how they did this was still unclear. Munafò et al. therefore set out to determine if the nucleoporins were indeed actively silencing the transposons, or if this was just a side effect of altered nuclear-cytosolic transport.
Experiments using cells grown from fruit fly ovaries revealed that depleting two specific nucleoporins, Nup54 and Nup58, re-activated transposons with minimal effects on most genes or the overall health of the cells. This suggests that Nup54 and Nup58 play a direct role in transposon silencing.
Further, detailed analysis of gene expression in Nup54- and Nup58-lacking cells revealed that the product of one gene, flamenco, was indeed affected. Normally, flamenco acts as a ‘master switch’ to turn off transposons. Without Nup54 and Nup58, the molecule encoded by flamenco could not reach its dedicated location in the cytosol, and thus could not carry out its task.
These results show that, far from being mere ‘doorkeepers’ for the nucleus, nucleoporins play important roles adapted to individual tissues in the body. Further research will help determine if the same is true for other organisms, and if these mechanisms can help understand human diseases.
The illustration is an artistic representation of the flamenco transcript (snake-like shape) exiting the nucleus and finding its way to the cytosol across an intricate mesh of nucleoporins. The drawing of the nucleoporins is inspired by the image accompanying the “Molecule of the Month” feature about the nuclear pore complex by David S. Goodsell and the RCSB PDB
Munafò M, Lawless VR, Passera A, MacMillan S, Bornelöv S, Haussmann IU, Soller M, Hannon GJ, Czech B. Channel Nuclear Pore Complex subunits are required for transposon silencing in Drosophila. Elife. 2021 Apr 15;10:e66321. doi: 10.7554/eLife.66321. Epub ahead of print. PMID: 33856346.
This article was originally published as an eLife digest for Munafò et al., 2021