Channel nuclear pore complex subunits are required for transposon silencing in Drosophila

Abstract

The Nuclear Pore Complex (NPC) is the principal gateway between nucleus and cytoplasm that enables exchange of macromolecular cargo. Composed of multiple copies of ~30 different nucleoporins (Nups), the NPC acts as a selective portal, interacting with factors which individually license passage of specific cargo classes. Here we show that two Nups of the inner channel, Nup54 and Nup58, are essential for transposon silencing via the PIWI-interacting RNA (piRNA) pathway in the Drosophila ovary. In ovarian follicle cells, loss of Nup54 and Nup58 results in compromised piRNA biogenesis exclusively from the flamenco locus, whereas knockdowns of other NPC subunits have widespread consequences. This provides evidence that some nucleoporins can acquire specialised roles in tissue-specific contexts. Our findings consolidate the idea that the NPC has functions beyond simply constituting a barrier to nuclear/cytoplasmic exchange, as genomic loci subjected to strong selective pressure can exploit NPC subunits to facilitate their expression.

Indel driven rapid evolution of core nuclear pore protein gene promoters

“…Given the role of channel Nups in piRNA meditated transposon silencing of the flamenco locus in the germline and their requirement for sexual differentiation (Munafo, et al 2021; Nallasivan, et al 2021), changes at one trait could cascade into the second leading to rapid phenotypic evolution and speciation. Intriguingly, mutations in cis -regulatory sequences of genes are often dominant whereas the majority of coding mutations are recessive (Pastinen, et al 2004; Ronald, et al 2005; Wittkopp, et al 2004) leading to different efficacy of selection (Stern 2000; Wilkins 2002; Wray, et al 2003).…”

“…Additionally, channel Nups have also been attributed a role in transposon silencing in the germline by facilitating processing of short piRNAs from long pre-curser RNAs of the flamenco locus (Munafo, et al 2021), indicating that the disruption to NPC regulation likely has pleiotropic effects.…”

“…In addition, a screen for sex-peptide insensitive mutants identified Nup54 functionality to be important for neuronal wiring of circuits involved in regulating post-mating behaviours (Nallasivan, et al 2021). Additionally, channel Nups have also been attributed a role in transposon silencing in the germline by facilitating processing of short piRNAs from long pre-curser RNAs of the flamenco locus (Munafo, et al 2021), indicating that the disruption to NPC regulation likely has pleiotropic effects.…”

Channel nuclear pore protein 54 directs sexual differentiation and neuronal wiring of female reproductive behaviors in Drosophila

“…In contrast, RNAi of Nup58 resulted in general lethality. Differences among channel Nups have also been seen in piRNA biogenesis of the flamenco locus [ 46 ]. Even though channel Nups form a complex, they could have individual roles in nucleo-cytoplasmic shuttling pathways, but alternatively, phenotypic differences could also be a result of the different strengths of the RNAi lines.…”

“…PIWI further interacts with ELYS at nuclear pores indicating that RNA export through nuclear pores is critical for transposon suppression [ 51 , 52 ]. In particular, channel Nups are required for piRNA biogenesis of the flamenco locus and through transposon silencing can impact on fecundity [ 46 ]. The driving forces behind the role of Nups in speciation clearly seem to go beyond hybrid sterility or lethality.…”