AGO2
GeneName
AGO2
Summary
AGO2, also known as PPD, hAgo2, or Argonaute-2, is a 97kDa protein that plays a pivotal role in the RNA interference pathway and is essential for the function of the RNA-induced silencing complex (RISC). It is predominantly expressed in the cytoplasm and nucleus, localised within various subcellular structures such as P-bodies, cytoplasmic ribonucleoprotein granules, and dendrites. AGO2 is involved in the binding and regulation of microRNAs (miRNAs) and small interfering RNAs (siRNAs), facilitating the cleavage of target mRNAs and thus modulating gene expression. Its functions extend to processes such as miRNA processing, gene silencing, and the regulation of mRNA stability, making it a crucial component in post-transcriptional regulation.
Importance
AGO2 is relevant to: - The study of gene regulation mechanisms through its role in miRNA and siRNA pathways, impacting various biological processes. - Cancer research, as aberrations in miRNA function and expression can lead to oncogenesis and tumour progression. - Neurobiology, given its involvement in synapse maturation and regulation of neuronal gene expression, which may influence neurodevelopmental and neurodegenerative conditions. - Developmental biology, due to its functions in post-embryonic development and trophoblast cell migration, which are critical for placental development and function.
Top Products
For researchers investigating AGO2, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-Argonaute-2 antibody (ab32381), which has garnered 478 citations, underscoring its reliability in Western blotting (WB) and immunohistochemistry (IHC). In addition, we offer the recombinant monoclonal antibody, Anti-Argonaute-2 antibody [EPR10411] (ab186733). This antibody has been validated in knockout models and is suitable for a broader range of applications, including WB, immunoprecipitation (IP), immunocytochemistry (ICC), IHC, and flow cytometry (FC). With 383 citations, it is a trusted choice for researchers seeking consistent performance across various experimental setups.
Abcam Product Citation Summary
The data indicates that AGO2 is frequently studied in human cell lines, particularly HEK293 and HEK293T, using Western blotting techniques. There is a notable focus on RNA editing, RNA interference, and the integrated RISC complex in these studies. Additionally, AGO2 is investigated in the context of nasopharyngeal carcinoma, highlighting its potential role in cancer biology.
Abcam Product Citation Table
Domain
The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).
Function
Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions.
(Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response.
Involvement in disease
Lessel-Kreienkamp syndrome
LESKRES
An autosomal dominant disorder characterized by global developmental delay, intellectual disability of variable degree, and speech and language delay apparent from infancy or early childhood. Behavioral disorders are observed in most patients. Additional variable features include seizures, hypotonia, gait abnormalities, visual and cardiac defects, and non-specific facial dysmorphism.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.
Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs) (PubMed:33184234, PubMed:33184237). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation (PubMed:33184234, PubMed:33184237). ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target (PubMed:33184237).
Phosphorylated. A phosphorylation cycle of C-terminal serine cluster (Ser-824-Ser-834) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target.
Phosphorylation at Ser-387 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage.
Sequence Similarities
Belongs to the argonaute family. Ago subfamily.
Cellular localization
- Cytoplasm
- P-body
- Nucleus
- Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.
Alternative names
EIF2C2, AGO2, Protein argonaute-2, Argonaute2, hAgo2, Argonaute RISC catalytic component 2, Eukaryotic translation initiation factor 2C 2, PAZ Piwi domain protein, Protein slicer, eIF-2C 2, eIF2C 2, PPD