In:
Cells Tissues Organs, S. Karger AG, Vol. 177, No. 3 ( 2004), p. 132-138
Abstract:
RNA interference (RNAi) is a powerful method that specifically suppresses gene expression in a sequence-dependent manner whose machinery is found in organisms from fungi to mammals. Mammalian cells have developed a sequence-independent system of gene suppression often induced by viral replication that includes the recognition of double-stranded RNA (dsRNA) through Toll-like receptor 3 (TLR3) and induction of type I interferon synthesis. Interferon activates the transcription of a set of genes including dsRNA-activated protein kinase that suppresses protein synthesis and 2′-5′-oligoadenylate synthetase, which generates a product that activates RNase L to cleave RNA in a sequence-independent manner. We observed that 21-bp dsRNA, a key mediator of RNAi, not only induces sequence-specific gene suppression, but also signals TLR3 to induce type I interferon and activates sequence-independent suppression of protein synthesis and enhancement of mRNA degradation. This sequence-independent suppression was demonstrated for both an exogenously administered reporter gene as well as during the targeting of viral genes in the course of acute herpes simplex virus type I infection of keratinocytes. As TLR3 is expressed by many primary cell types and cell lines, this sequence-independent suppression should be considered in the design of experiments using small interfering RNA-mediated gene suppression.
Type of Medium:
Online Resource
ISSN:
1422-6405
,
1422-6421
Language:
English
Publisher:
S. Karger AG
Publication Date:
2004
detail.hit.zdb_id:
1481840-1
SSG:
12
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