Article

Development of resistance to RNAi in mammalian cells.

HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 10S 255, Bethesda, MD 20892, USA.
Annals of the New York Academy of Sciences (impact factor: 3.15). 12/2005; 1058:105-18. DOI:10.1196/annals.1359.019 pp.105-18
Source: PubMed

ABSTRACT The discovery of RNA interference (RNAi) in C. elegans and in plants has revolutionized current approaches to biology and medicine. RNAi silences genes in a sequence-specific manner through the actions of small pieces of double-stranded RNAs (siRNAs and miRNAs). RNAi has been found as a widespread natural phenomenon in eukaryotic cells and is also being used as a powerful experimental tool to explore gene function. Most importantly, it has many potential therapeutic applications. Viral gene-specific siRNAs are theoretically very promising antiviral inhibitors and have been examined in a broad range of medically important viruses. However, many RNA viruses escape RNAi-mediated suppression by counteracting the RNAi machinery through mutation of the targeted region, by encoding viral suppressors, or both. DNA viruses also counteract the RNAi machinery, preferentially using viral suppressors. Cellular factors may also contribute to RNAi resistance; ADAR1 was the first cellular factor found to be responsible for editing-mediated RNAi resistance. Because siRNAs can be used as potent small-molecule inhibitors of any cellular gene, the best way for a cell to maintain expression of essential genes for its long-term survival is to develop a program to resist the detrimental effects of RNAi.

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Keywords

broad range
 
C. elegans
 
Cellular factors
 
cellular gene
 
detrimental effects
 
DNA viruses
 
editing-mediated RNAi resistance
 
encoding viral suppressors
 
first cellular factor
 
potent small-molecule inhibitors
 
potential therapeutic applications
 
powerful experimental tool
 
RNA interference
 
RNA viruses
 
RNAi machinery
 
RNAi silences genes
 
targeted region
 
Viral gene-specific siRNAs
 
viral suppressors
 
widespread natural phenomenon
 

Zhi-Ming Zheng