ZC3HC1 has many functions distinct from TPR and is dispensable for TPR localisation to the nuclear basket.

Background: The nuclear basket is a 'fishtrap'-like structure on the nucleoplasmic face of the nuclear pore complex which has been implicated in diverse functions including RNA export, heterochromatin organisation, and mitosis. Recently, a novel component of the nuclear basket, ZC3HC1, has been described. The localisation of ZC3HC1 to nuclear pores has been reported to occur reciprocally with TPR, a major structural component of the nuclear basket. Methods: Using siRNA-mediated knock down, immunofluorescence and RNA sequencing we compare the consequences of depleting two proteins of the nuclear pore basket - TPR and ZC3HC1. Results: We show that in human fibroblasts, although ZC3HC1 localisation to nuclear pores is TPR-dependent, TPR remains localised to pores when ZC3HC1 is depleted. Consistent with this, during oncogene-induced senescence, knockdown of ZC3HC1 does not compromise the formation of senescence-associated heterochromatin foci or activation of the senescence-associated secretory phenotype, which are both known to depend on the presence of TPR at the nuclear basket. We demonstrate that knockdown of TPR and ZC3HC1, although partially overlapping, also have many distinct transcriptional features. Conclusions: Our results suggest that there is limited overlap in function between these two nuclear basket proteins in human diploid fibroblasts.