AGO3 gene

The AGO3 gene (AGO3 stands for: Argonaute RISC Catalytic Component 3) is a protein-coding gene located on chromosome 1p34.3. Two transcript variants encoding different isoforms have been identified for this gene. An important paralog of this gene is AGO1.

The AGO3 gene encodes a member of the Argonaute family of proteins that play a role in RNA interference. The encoded protein is highly basic, contains a PAZ domain and a PIWI domain, and may play a role in short-interfering RNA-mediated gene silencing. The AGO3 gene is located on chromosome 1 in a tandem cluster with closely related family members such as Argonaute 4 and eukaryotic translation initiation factor 2C, 1.

It is thought to be involved in the stabilization of small RNA derivatives (siRNA) derived from processed Alu repeats transcribed by RNA polymerase III containing a DR2 retinoic acid response element (RARE) in stem cells, and in the subsequent siRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruitment of an mRNA decapping complex involving EDC4. Possesses RNA slicer activity, but only for selected RNAs with 5'- and 3'-flanking sequences to the region of guide-target complementarity (Park MS et al. 2017).

Diseases associated with AGO3 include cartilage-hair hypoplasia (Cartilage-Hair Hypoplasia/CHH/ OMIM:250250/Orphanet:ORPHA175). Related pathways include transcriptional regulation by MECP2 and organization of cell assemblies.

AGO3 and cervical carcinoma: RNA profiling of 306 cervical cancer tissues and 13 normal samples showed that AGO3 was significantly upregulated in cervical cancer and that AGO3 expression was negatively associated with the outcome of cervical cancer patients. Deletion of AGO3 significantly inhibits the growth and mobility of cervical cancer cells. Elimination of AGO3 via inactivation of the Wnt/β-catenin signaling pathway exerts a suppressive effect on cell behavior (Pan L et al. 2021).

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3. Pan L et al. (2021) Argonaute 3 (AGO3) promotes malignancy potential of cervical cancer via regulation of Wnt/β-catenin signaling pathway. Reprod Biol 21:100479
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