Blood circulating miRNAs are contained in microvesicles known as exosomes or are associated with
Argonaute 2 complexes and, as a consequence, are protected from degradation (6,24).
Mammalian
Argonaute 2 (Ago2) protein is the key player of RNA-induced silencing complexes, regulating gene function through RNA interference.
Huang et al., "
Argonaute 2 complexes selectively protect the circulating microRNAs in cell-secreted microvesicles," PLoS One, vol.
RISC consists in RNA helicase A and proteins such as
argonaute 2 and TRBP that will facilitate the binding of miRNA to its mRNA target [57, 58].
White et al., "AUF1 promotes let-7b loading on
Argonaute 2," Genes & Development, vol.
Huang et al., "Dephosphorylation of tyrosine 393 in
argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence," Molecular Cell, vol.
CiRS-7 can be cleaved by miR-671 and its associated Argonaute protein, whereas it is not cleaved by miR-7 and
Argonaute 2 [298,299].
Apart from these classical pathways (gap junction channels, apoptosis bodies, and synaptic cleft), exosomes are proposed to carry functional miRNAs coupled to the enzyme
Argonaute 2 and migrate into the surrounding cells [17].
Argonaute 2 complexes carry a population Of circulating microRNAs independent of vesicles in human plasma.
Specific miRNAs binding to viral RNA during HRV infection is demonstrated by co-immunoprecipitate test with
argonaute 2 protein.
Most perfectly complimentary sequences (like most siRNAs) allow for site-specific cleavage of the target mRNAs by
argonaute 2, an RNAse III enzyme, at predictable and verifiable locations, namely, distal to the 10th nucleotide from the 5'-end of the guide strand [104,108].
The knockouts can be either a miRNA itself or key miRNA processing factors such as Drosha, Dicer, and
argonaute 2 (Ago2).