Non-targeting SiRNA Induces NPGPx Expression to Cooperate with Exoribonuclease XRN2 for Releasing the Stress

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2011 Sep 13

PMID 21908404

Citations 10

Authors

Pei-Chi Wei

Wen-Ting Lo

Mei-I Su

Jin-Yuh Shew

Wen-Hwa Lee

Affiliations

Soon will be listed here.

Abstract

Short interfering RNAs (siRNAs) target specific mRNAs for their degradation mediated by RNA-induced silencing complex (RISC). Persistent activation of siRNA-RISC frequently leads to non-targeting toxicity. However, how cells mediate this stress remains elusive. In this communication, we found that the presence of non-targeting siRNA selectively induced the expression of an endoplasmic reticulum (ER)-resident protein, non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), but not other ER-stress proteins including GRP78, Calnexin and XBP1. Cells suffering from constant non-targeting siRNA stress grew slower and prolonged G1 phase, while NPGPx-depleted cells accumulated mature non-targeting siRNA and underwent apoptosis. Upon the stress, NPGPx covalently bound to exoribonuclease XRN2, facilitating XRN2 to remove accumulated non-targeting siRNA. These results suggest that NPGPx serves as a novel responder to non-targeting siRNA-induced stress in facilitating XRN2 to release the non-targeting siRNA accumulation.

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