AGO1

AGO1 is a member of the Argonaute family of proteins that mediate RNA interference and related gene-silencing pathways in eukaryotic cells. In humans, four Argonaute proteins (AGO1–AGO4) participate in RNA-induced silencing complexes (RISCs) that use small RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) to regulate gene expression.

Structure and mechanism: Argonaute proteins share a tripartite domain architecture that includes the PAZ, MID, and PIWI domains. The PAZ domain binds the 3’ end of the guide small RNA, the MID domain binds the 5’ phosphate, and the PIWI domain resembles an RNase H–like region. AGO1 binds guide RNAs and, as part of RISC, pairs with target mRNAs to mediate silencing. In contrast to AGO2, which has robust endonuclease (slicer) activity, AGO1 is generally catalytically inactive for RNA cleavage; silencing is mainly achieved through translational repression, deadenylation, or decapping in collaboration with other factors.

Expression and localization: AGO1 is expressed in various tissues and is predominantly cytoplasmic, where it partners with miRNAs/siRNAs and effector proteins. Some studies also report nuclear localization under certain conditions, suggesting additional roles in transcriptional or chromatin-related regulation.

Biological significance: The AGO1–AGO4 proteins are central to post-transcriptional gene regulation by miRNAs and siRNAs. Dysregulation of Argonaute proteins has been observed in diverse contexts, including development and cancer, reflecting their essential role in controlling gene expression and cellular function.