Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-18
pubmed:abstractText
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 <approximately 30 base pairs to avoid nonspecific effects that arise from inducing the cellular double-stranded RNA (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.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-10349646, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-10461204, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-10557102, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-10626894, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-10871365, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-11238371, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-11373684, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-11481446, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-11487589, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12016302, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12016303, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12110901, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12408822, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12670898, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12746500, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12754523, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-12796781, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-7912826, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-8557029, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-9625760, http://linkedlifedata.com/resource/pubmed/commentcorrection/14681580-9861020
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1355-8382
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12-8
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs).
pubmed:affiliation
Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't