dsRNA Double-stranded RNA; generally refers to long or full length RNA duplexes. These large dsRNA initiate a general host cell shutdown in most mammalian cell types; the cells subsequently begin to decrease their expression of non-targeted genes and ultimately undergo apoptosis.
RISC RNA-induced silencing complex; this is the proposed multi-protein complex that acts to bring the antisense strand of the siRNA and the cellular mRNA together. An endonucleolytic activity associated with the RISC cleaves the mRNA, which is then released and degraded.
shRNA Short hairpin RNA; also short interfering hairpin; the shRNA contains sense and antisense sequences from a target gene connected by a loop and is expressed in mammalian cells from a vector by a pol III type promoter. The shRNA is transported from the nucleus into the cytoplasm, where Dicer processes it. Once in the cell the shRNA can decrease the expression of a gene with complementary sequences by RNAi.
Pol III promoter A pol III promoter, typically U6 or H1, is used to drive the production of shRNA. U6 and H1 pol III promoters have all the elements required for the initiation of transcription upstream of a defined start site and terminate transcription at 4 or more T's.
U6 promoter A pol III type promoter that allows the production of shRNA with a defined end (see also Pol III promoter).
Non-specific effects These effects are a generalized toxic cellular response, and has been noted when long dsRNA is introduced into mammalian cells. This has also been identified as occurring in some cases from the introduction of siRNA or d-siRNA sequences. The activation of certain genes in the PKR or the 5'OAS pathway can occur, and this stimulates an interferon type response in the cell. This can lead to general host cell shutdown and apoptosis.
Off-target effects These effects occur when one or a few genes not specifically targeted show loss of gene function following the introduction of an siRNA or d-siRNA pool. The sense strand of an siRNA may be able to initiate a loss of function response from an unrelated gene. Off target effects may also refer to a secondary effect of the antisense strand of a specific siRNA where it has the appropriate homology to knockdown the expression of another related gene that carries the same sequence.
PTGS Post transcriptional gene silencing; A phenomenon first identified in plants that has also been shown to occur in animals. Although PTGS was initially described as an endogenous method for viral defense and transposon silencing, it has now emerged as an exciting new research tool, RNA interference.
Cosuppression Refers to the specific case of gene silencing in which RNA from a transgene and a homologous endogenous gene are suppressed at the same time.
Quelling Cosuppression as described in Neurospora crassa- this term has only been used to describe silencing of a gene in fungi.
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