Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Department of Life Science, Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, United Kingdom.
Elife. 2021 Apr 15;10:e66321. doi: 10.7554/eLife.66321.
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 ovary. In ovarian follicle cells, loss of Nup54 and Nup58 results in compromised piRNA biogenesis exclusively from the locus, whereas knockdowns of other NPC subunits have widespread consequences. This provides evidence that some Nups 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.
核孔复合体(NPC)是细胞核和细胞质之间的主要通道,允许大分子货物交换。NPC 由~30 种不同的核孔蛋白(Nups)的多个拷贝组成,作为一个选择性门户,与单独许可特定货物类别的通过的因素相互作用。在这里,我们表明,两个内通道的 Nups,Nup54 和 Nup58,对于通过 PIWI 相互作用 RNA(piRNA)途径在卵巢中沉默转座子是必不可少的。在卵巢滤泡细胞中,Nup54 和 Nup58 的缺失导致仅从 基因座产生受损的 piRNA,而其他 NPC 亚基的敲低则具有广泛的后果。这提供了一些 Nups 可以在组织特异性上下文中获得专门作用的证据。我们的研究结果巩固了 NPC 的功能不仅仅是简单地构成核/细胞质交换的障碍的观点,因为受到强烈选择压力的基因组位点可以利用 NPC 亚基来促进它们的表达。