Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof-of-concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR-193a (Trp/Ago2/miR-193a) is identified. Trp binds miR-193a-3p and interacts with Ago2. Trp/Ago2/miR-193a increases miR-193a-3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR-103 and miR-107 in the Trp complex enhance miR-193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR-193a complex interacts with Trp-binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR-193a-3p complex is more efficient than miR-193a-3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA-induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336974PMC
http://dx.doi.org/10.1002/advs.202307937DOI Listing

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