# Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression

## TL;DR

This study shows how two cellular complexes, NEXT and HUSH, work together to suppress harmful transposable element RNA in embryonic stem cells.

## Contribution

The paper reveals a physical and functional link between NEXT and HUSH complexes in controlling transposable element RNA.

## Key findings

- ZCCHC8 knockout increases transposable element RNA levels in embryonic stem cells.
- HUSH recruits NEXT to chromatin at transposable element loci bound by MPP8.
- NEXT and HUSH suppress different types of transposable element transcripts.

## Abstract

Transposable elements (TEs) are widespread genetic parasites known to be kept under tight transcriptional control. Here, we describe a functional connection between the mouse-orthologous “nuclear exosome targeting” (NEXT) and “human silencing hub” (HUSH) complexes, involved in nuclear RNA decay and the epigenetic silencing of TEs, respectively. Knocking out the NEXT component ZCCHC8 in embryonic stem cells results in elevated TE RNA levels. We identify a physical interaction between ZCCHC8 and the MPP8 protein of HUSH and establish that HUSH recruits NEXT to chromatin at MPP8-bound TE loci. However, while NEXT and HUSH both dampen TE RNA expression, their activities predominantly affect shorter non-polyadenylated and full-length polyadenylated transcripts, respectively. Indeed, our data suggest that the repressive action of HUSH promotes a condition favoring NEXT RNA decay activity. In this way, transcriptional and post-transcriptional machineries synergize to suppress the genotoxic potential of TE RNAs.

Garland et al. report a physical and functional connection between the NEXT complex, involved in RNA decay, and the HUSH complex, involved in chromatin regulation. Together, NEXT and HUSH cooperate to control transposable element (TE) RNA expression in embryonic stem cells, suppressing pA− and pA+ transcripts, respectively.