# Loss of Dicer1 in mouse embryonic fibroblasts impairs ER stress-induced apoptosis

## TL;DR

This study shows that loss of Dicer1 in mouse cells reduces ER stress-induced cell death and alters UPR responses.

## Contribution

The study reveals a novel role for Dicer-dependent miRNA biogenesis in regulating ER stress and apoptosis.

## Key findings

- Dicer deficiency attenuates ER stress-induced caspase activation and apoptosis.
- ER stress responses like GRP78 and HERP are enhanced in Dicer-deficient cells.
- BIM and MCL1 expression is altered in Dicer-null cells under ER stress.

## Abstract

The endoplasmic reticulum (ER) is the site of folding for membrane and secreted proteins. Accumulation of unfolded or misfolded proteins in the ER triggers the unfolded protein response (UPR). The UPR can promote survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. However, when ER stress is acute or prolonged cells undergo apoptosis. In this study we sought to determine the effect of globally compromised microRNA biogenesis on the UPR and ER stress-induced apoptosis

Here we report the role of Dicer-dependent miRNA biogenesis during the UPR and ER stress-induced apoptosis. We show that ER stress-induced caspase activation and apoptosis is attenuated in Dicer deficient fibroblasts. ER stress-mediated induction of GRP78, the key ER resident chaperone, and also HERP, an important component of ER-associated degradation, are significantly increased in Dicer deficient cells. Expression of the BCL-2 family members BIM and MCL1 were significantly higher in Dicer-null fibroblasts. However, ER stress-mediated induction of pro-apoptotic BH3 only protein BIM was compromised in Dicer mutant cells.

These observations demonstrate key roles for Dicer in the UPR and implicate miRNAs as critical components of UPR.