Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to includeAGO2 bound to a short guide RNA such as a microRNA (miRNA) or shortinterfering RNA (siRNA). These guide RNAs direct RISC to complementarymRNAs that are targets for RISC-mediated gene silencing. The precisemechanism of gene silencing depends on the degree of complementaritybetween the miRNA or siRNA and its target. Binding of RISC to aperfectly complementary mRNA generally results in silencing due toendonucleolytic cleavage of the mRNA specifically by AGO2. Binding ofRISC to a partially complementary mRNA results in silencing throughinhibition of translation, and this is independent of endonucleaseactivity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of thetranslation initiation factor eIF4-E. May also inhibit translationinitiation via interaction with EIF6, which itself binds to the 60Sribosomal subunit and prevents its association with the 40S ribosomalsubunit. The inhibition of translational initiation leads to theaccumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some casesRISC-mediated translational repression is also observed for miRNAs thatperfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growthconditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serumstarvation. Also required for transcriptional gene silencing (TGS), inwhich short RNAs known as antigene RNAs or agRNAs direct thetranscriptional repression of complementary promoter regions. [1-23]

MYSGAGPALAPPAPPPPIQGYAFKPPPRPDFGTSGRTIKLQANFFEMDIPKIDIYHYELDIKPEKCPRRVNREIVEHMVQHFKTQIFGDRKPVFDGRKNLYTAMPLPIGRDKVELEVTLPGEGKDRIFKVSIKWVSCVSLQALHDALSGRLPSVPFETIQALDVVMRHLPSMRYTPVGRSFFTASEGCSNPLGGGREVWFGFHQSVRPSLWKMMLNIDVSATAFYKAQPVIEFVCEVLDFKSIEEQQKPLTDSQRVKFTKEIKGLKVEITHCGQMKRKYRVCNVTRRPASHQTFPLQQESGQTVECTVAQYFKDRHKLVLRYPHLPCLQVGQEQKHTYLPLEVCNIVAGQRCIKKLTDNQTSTMIRATARSAPDRQEEISKLMRSASFNTDPYVREFGIMVKDEMTDVTGRVLQPPSILYGGRNKAIATPVQGVWDMRNKQFHTGIEIKVWAIACFAPQRQCTEVHLKSFTEQLRKISRDAGMPIQGQPCFCKYAQGADSVEPMFRHLKNTYAGLQLVVVILPGKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLKINVKLGGVNNILLPQGRPPVFQQPVIFLGADVTHPPAGDGKKPSIAAVVGSMDAHPNRYCATVRVQQHRQEIIQDLAAMVRELLIQFYKSTRFKPTRIIFYRDGVSEGQFQQVLHHELLAIREACIKLEKDYQPGITFIVVQKRHHTRLFCTDKNERVGKSGNIPAGTTVDTKITHPTEFDFYLCSHAGIQGTSRPSHYHVLWDDNRFSSDELQILTYQLCHTYVRCTRSVSIPAPAYYAHLVAFRARYHLVDKEHDSAEGSHTSGQSNGRDHQALAKAVQVHQDTLRTMYFA