exRNA mechanism of action and biogenesis (WP2805)

Homo sapiens

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]

Authors

Kristina Hanspers

Activity

last edited

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Organisms

Homo sapiens

Communities

ExRNA

Annotations

Pathway Ontology

microRNA pathway

Participants

Label Type Compact URI Comment
HDL Metabolite chebi:39025
DICER1 GeneProduct ncbigene:23405
XPO5 GeneProduct ncbigene:57510
Drosha GeneProduct ncbigene:29102
ERI1 GeneProduct ensembl:ENSG00000104626
DGCR8 GeneProduct ensembl:ENSG00000128191
AGO2 GeneProduct ensembl:ENSG00000123908
DICER1 GeneProduct ncbigene:23405

References

  1. Liposomal siRNA nanocarriers for cancer therapy. Ozpolat B, Sood AK, Lopez-Berestein G. Adv Drug Deliv Rev. 2014 Feb;66:110–6. PubMed Europe PMC Scholia
  2. Eri1: a conserved enzyme at the crossroads of multiple RNA-processing pathways. Thomas MF, L’Etoile ND, Ansel KM. Trends Genet. 2014 Jul;30(7):298–307. PubMed Europe PMC Scholia
  3. Cellular and viral microRNAs in sepsis: mechanisms of action and clinical applications. Giza DE, Fuentes-Mattei E, Bullock MD, Tudor S, Goblirsch MJ, Fabbri M, et al. Cell Death Differ. 2016 Dec;23(12):1906–18. PubMed Europe PMC Scholia