miRISC is a multi-protein assembly that identifies mRNAs targeted for reppression using microRNAs (miRNAs). In vitro and in living cells, 29576456 demonstrated that two core protein components of human miRISC, Argonaute2 (Ago2) and TNRC6B, condense into phase-separated droplets.
Formation, Composition & dynamics (Assembly and disassembly)
Relation to human diseases
Proteome
Formation, Composition & dynamics (Assembly and disassembly)
The glycine/tryptophan (GW)-rich domain of TNRC6B interacts multivalently with three equally spaced tryptophan-binding pockets in the Ago2 PIWI domain, promoting miRISC phase separation. Deadenylation factors are recruited and target RNAs are sequestered from the bulk solution by miRISC droplets produced in vitro. The rapid deadenylation of target RNAs coupled to Ago2 coincides with the condensation of miRISC (29576456).
Relation to human diseases
33215742 shows the role of miRISC in cancer.
32118035 discussed the role of miRISC in neuronal development.
References
Sheu-Gruttadauria J, MacRae IJ. Phase Transitions in the Assembly and Function of Human miRISC. Cell. 2018 May 3;173(4):946-957.e16. doi: 10.1016/j.cell.2018.02.051. Epub 2018 Mar 22. PMID: 29576456; PMCID: PMC5935535.
Shin E, Jin H, Suh DS, Luo Y, Ha HJ, Kim TH, Hahn Y, Hyun S, Lee K, Bae J. An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2. EMBO J. 2020 Dec 15;39(24):e104719. doi: 10.15252/embj.2020104719. Epub 2020 Nov 20. Erratum in: EMBO J. 2021 Aug 16;40(16):e108163. PMID: 33215742; PMCID: PMC7737606.
Nawalpuri B, Ravindran S, Muddashetty RS. The Role of Dynamic miRISC During Neuronal Development. Front Mol Biosci. 2020 Jan 31;7:8. doi: 10.3389/fmolb.2020.00008. PMID: 32118035; PMCID: PMC7025485.