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For example, human pre-miRNA 92b adopts a G-quadruplex structure which is resistant to the Dicer mediated cleavage in the cytoplasm. [75] Although either strand of the duplex may potentially act as a functional miRNA, only one strand is usually incorporated into the RNA-induced silencing complex (RISC) where the miRNA and its mRNA target interact.
RNA silencing describes several mechanistically related pathways which are involved in controlling and regulating gene expression. [5] [6] [7] RNA silencing pathways are associated with the regulatory activity of small non-coding RNAs (approximately 20–30 nucleotides in length) that function as factors involved in inactivating homologous sequences, promoting endonuclease activity ...
Some RISCs are able to directly target the genome by recruiting histone methyltransferases to form heterochromatin at the gene locus, silencing the gene. These RISCs take the form of a RNA-induced transcriptional silencing complex (RITS). The best studied example is with the yeast RITS. [1] [23] [24]
Another frequently cited example of virus resistance mediated by gene silencing involves papaya, where the Hawaiian papaya industry was rescued by virus-resistant GM papayas produced and licensed by university researchers rather than a large corporation. [45]
AGO2 (grey) in complex with a microRNA (light blue) and its target mRNA (dark blue) In humans, there are eight AGO family members, some of which are investigated intensively. However, even though AGO1–4 are capable of loading miRNA, endonuclease activity and thus RNAi-dependent gene silencing exclusively belongs to AGO2.
A miRNA is expressed from a much longer RNA-coding gene as a primary transcript known as a pri-miRNA which is processed, in the cell nucleus, to a 70-nucleotide stem-loop structure called a pre-miRNA by the microprocessor complex. This complex consists of an RNase III enzyme called Drosha and a dsRNA-binding protein DGCR8.
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20–24 base pairs in length, similar to microRNA (miRNA), and operating within the RNA interference (RNAi) pathway.
By decreasing the levels of p300, the expression of IFN-β, ISG15, IL-1β and IL6 is impaired, resulting in the net suppression of antiviral immunity. miR-132 is only transiently induced following infection; the silencing of p300 results in a reduction in CREB-mediated transcription from the miR-212/132 cluster, thus forming a negative feedback ...