exRNA mechanism of action and biogenesis (WP2805)

The process of RNA-interference in eukaryotic cells. Long precursor microRNA (miRNA), called pri-miRNA, is cleaved by RNase III endonuclease (Drosha) into pieces of approximately 70 nucleotides each (called pre-miRNA) in the nucleus. Following transportation into the cytoplasm by exportin 5 another RNase III endonuclease (Dicer) cleaves it into mature miRNA segments. Degradation of messenger RNA (mRNA) and translational repression occurs after miRNA binds to the RNA-induced silencing complex (RISC). Cytoplasmic long double-stranded RNA (dsRNA) is cleaved by Dicer into small interfering RNA (siRNA), which is incorporated into RISC, resulting in the cleavage and degradation of specific target mRNA. Synthetic double-stranded siRNA is not processed by Dicer and directly incorporated by the RISC. After cleavage by Dicer, mature miRNAs can also be released out of cells in exosomes, microvesicles or apoptotic bodies, or bond to some high-density lipoprotein (HDL) and Argonaute protein 2 (Ago2). Viral miRNAs exported from the nucleus are processed in the same way. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2805 CPTAC Assay Portal]

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