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

## TL;DR

This paper shows that ZC3HC1 and TPR, two proteins at nuclear pores, have distinct roles and ZC3HC1 doesn't affect TPR's placement.

## Contribution

It reveals ZC3HC1's function is distinct from TPR and not essential for TPR's localization in human fibroblasts.

## Key findings

- ZC3HC1 depends on TPR for its localization to nuclear pores.
- TPR localizes to pores regardless of ZC3HC1 presence.
- TPR and ZC3HC1 have distinct transcriptional effects when knocked down.

## Abstract

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.

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.

We show that in human fibroblasts, although ZC3HC1 localisation to nuclear pores is TPR-dependent, TPR localises to pores regardless of the presence of ZC3HC1. We demonstrate that knockdown of TPR and ZC3HC1 produce distinct transcriptional profiles.

Our results suggest that there is little overlap in function between these two nuclear basket proteins in human diploid fibroblasts.

Nuclear pores are structures critical for the regulating how molecules get into and out of the nucleus of our cells. They provide a channel through which selected cargoes are transported. These cargoes include the messenger RNAs that carry the information from DNA in the nucleus to make proteins in the cell cytoplasm. On the nuclear side of the nuclear pore, there is a poorly understood structure called the nuclear basket. This paper explores two proteins called TPR and ZC3HC1 that localise at the nuclear basket. Exploring the function of these two proteins, this paper shows that whilst TPR is important for the export of certain classes of messenger RNA, ZC3HC1 is not. This suggests that these two proteins of the nuclear basket have quite different functions. In addition, we show that, whilst ZC3HC1 depends on TPR for its localisation at nuclear pores, the reverse is not the case - TPR localisation appears to be independent of ZC3HC1.