AGO2

This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Full Name

Argonaute 2, RISC Catalytic Component

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 (TNF-alpha) 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.

Biological Process

Gene silencing by RNA
Intracellular receptor signaling pathway
miRNA loading onto RISC involved in gene silencing by miRNA
miRNA mediated inhibition of translation
miRNA metabolic process
mRNA cleavage involved in gene silencing by miRNA
mRNA cleavage involved in gene silencing by siRNA
Negative regulation of amyloid precursor protein biosynthetic process
Negative regulation of gene expression
Negative regulation of translational initiation
Positive regulation of angiogenesis
Positive regulation of gene expression
Positive regulation of miRNA mediated inhibition of translation
Positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Positive regulation of nuclear-transcribed mRNA poly(A) tail shortening
Positive regulation of transcription by RNA polymerase II
Positive regulation of translation, ncRNA-mediated
Positive regulation of trophoblast cell migration
Post-embryonic development
Post-transcriptional gene silencing by RNA
Pre-miRNA processing
Production of miRNAs involved in gene silencing by miRNA
Production of siRNA involved in RNA interference
Regulation of gene silencing by miRNA
RNA secondary structure unwinding
siRNA loading onto RISC involved in RNA interference
Translation
Wnt signaling pathway, calcium modulating pathway

Cellular Location

Nucleus; P-body. Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.

PTM

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). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target.