Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs)
UMass Chan Affiliations
Program in Gene Function and ExpressionHoward Hughes Medical Institute, Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2003-12-19Keywords
Gene Expression ProfilingGene Expression Regulation
*Gene Silencing
Hela Cells
Humans
Luciferases
Oligonucleotide Array Sequence Analysis
*RNA Interference
RNA, Double-Stranded
RNA, Neoplasm
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
RNA interference is an evolutionarily conserved process in which expression of a specific gene is post-transcriptionally inhibited by a small interfering RNA (siRNA), which recognizes a complementary mRNA and induces its degradation. Currently, RNA interference is being used extensively to inhibit expression of specific genes for experimental and therapeutic purposes. For applications in mammalian cells, siRNAs are designed to be (dsRNA)-dependent protein kinase (PKR) response. Here we perform expression profiling in mammalian tissue-culture cells treated under standard conditions with conventional 21-bp siRNAs and find, unexpectedly, that >1000 genes involved in diverse cellular functions are nonspecifically stimulated or repressed. The effects on gene expression are dependent upon siRNA concentration and are stable throughout the course of siRNA treatment. Our results can be explained by previous studies showing that dsRNAs can affect multiple signaling and transcription pathways in addition to PKR. The potential for this widespread, nonspecific effect on mammalian gene expression must be carefully considered in the design of siRNA experiments and therapeutic applications.Source
RNA. 2004 Jan;10(1):12-8.