Adverse effects induced by short hairpin RNA expression in porcine fetal fibroblasts

被引：47

作者：

Stewart, Candace K. ^{[1
]}

Li, Julang ^{[1
]}

Golovan, Serguei P. ^{[1
]}

机构：

[1] Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 370卷 / 01期

基金：

加拿大自然科学与工程研究理事会;

关键词：

RNA interference; shRNA; myostatin; interferon; MicroRNA;

D O I：

10.1016/j.bbrc.2008.03.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RNA interference is a recent, gene silencing technique that could be extremely valuable in studying gene function, treating diseases, and developing novel animal models for human diseases. Here, we investigated the feasibility of applying shRNA-mediated RNA interference in fetal fibroblasts for silencing of the myostatin gene and investigate adverse effects of RNAi We report that up to 97% silencing of myostatin mRNA was achieved using shRNA constructs in transiently and stably transfected fetal fibroblasts (p < 0.05). At the same time we also demonstrate that high level of shRNA expression resulted in 10- to 1000-fold induction of interferon responsive genes (OAS1, IFN-beta) (p < 0.05). In addition we also report novel adverse effect of shRNA expression in stably transfected cells-interference with microRNA processing/transport which led to 500-fold increase in the level of miR21 precursors (p < 0.05). Reduction of these side effects will be essential to obtain long term stable RNAi silencing. Crown Copyright (c) 2008 Published by Elsevier Inc. All rights reserved.

引用

页码：113 / 117

页数：5

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