exRNA mechanism of action and biogenesis (Homo sapiens)

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2, 3ExosomeNucleusMicrovesicleNucleusTranslational repressionor mRNA degradationTarget mRNAViral miRNARNA-induced silencing complexXPO5dsRNApre-miRNAAGO2ERI1DGCR8DICER1DroshaHDLmiRNA1DICER1pri-miRNAmRNA cleavageand degradationsiRNARISCRISCTarget mRNAexo-siRNARISCexo-siRNAExogenous small interfering RNAssiRNAsiRNAExosomesiRNAsiRNAApoptoticbodysiRNAsiRNA


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 CPTAC Assay Portal

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Ontology Terms



  1. Thomas MF, L'Etoile ND, Ansel KM; ''Eri1: a conserved enzyme at the crossroads of multiple RNA-processing pathways.''; Trends Genet, 2014 PubMed Europe PMC Scholia
  2. Giza DE, Fuentes-Mattei E, Bullock MD, Tudor S, Goblirsch MJ, Fabbri M, Lupu F, Yeung SJ, Vasilescu C, Calin GA; ''Cellular and viral microRNAs in sepsis: mechanisms of action and clinical applications.''; Cell Death Differ, 2016 PubMed Europe PMC Scholia
  3. Ozpolat B, Sood AK, Lopez-Berestein G; ''Liposomal siRNA nanocarriers for cancer therapy.''; Adv Drug Deliv Rev, 2014 PubMed Europe PMC Scholia


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106523view23:44, 5 September 2019KhanspersModified description
105799view22:49, 15 August 2019KhanspersModified description
102224view21:03, 11 December 2018Khanspersdecreased board height
102223view21:01, 11 December 2018Khansperscondensed layout
99075view00:08, 30 October 2018KhanspersModified title
99033view21:57, 24 October 2018KhanspersModified title
99032view21:54, 24 October 2018KhanspersOntology Term : 'PW:0001161' removed !
99031view21:54, 24 October 2018KhanspersOntology Term : 'microRNA pathway' added !
99030view21:53, 24 October 2018KhanspersModified title
99029view21:52, 24 October 2018Khanspers
99028view21:51, 24 October 2018KhanspersModified description
99027view21:45, 24 October 2018KhanspersModified title
99026view21:45, 24 October 2018KhanspersAdded info from Giza et al
81654view19:46, 21 August 2015Khanspersfixed unconnected interaction
78493view10:28, 7 January 2015MaintBotadded missing graphIds
77709view23:56, 14 October 2014KhanspersAdded ERI1
75282view23:59, 13 May 2014KhanspersOntology Term : 'RNA degradation pathway' added !
75281view23:57, 13 May 2014KhanspersModified description
75280view23:56, 13 May 2014KhanspersModified title
75279view23:56, 13 May 2014KhanspersModified title
75278view23:55, 13 May 2014KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
AGO2GeneProductENSG00000123908 (Ensembl)
DGCR8GeneProductENSG00000128191 (Ensembl)
DICER1GeneProduct23405 (Entrez Gene)
DroshaGeneProduct29102 (Entrez Gene)
ERI1GeneProductENSG00000104626 (Ensembl)
HDLMetaboliteCHEBI:39025 (ChEBI)
XPO5GeneProduct57510 (Entrez Gene)

Annotated Interactions

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