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Generation of mirna
In nucleus inflammation can induce transcription of polII and the primirna transcript. This is then processed by factors such as p53 which is also induced by inflammation. This processed transcript is then exported out of the nucleus by exportin5. It is then further processed by dicer which is regulated by stress and inflammation. (Cytokines can also turn off dicer- self inhibition). This processing results in an mirna duplex. One strand is readily digested whereas the other strand star strand guides a risc complex to the target mrna. This can then be localised in a stress granule by importin 8. Stress granules are then stimulated in times of stress.
Hsc
Mir221, 1966 and 126 are implicated in hsc development.
Mirnas and innate response
Mir223 controls neutrophils development and activation. Deficiency of mir223 results in increased capacity to undergo oxidative burst. Found increased in patients with ibd. Controls nlrp3 inflammasome formation so prevents il1beta production. Regulates innate ir during intestinal inflamm.
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