APOBEC3G Inhibits MicroRNA-mediated Repression of Translation by Interfering with the Interaction between Argonaute-2 and MOV10

作者：Liu, Chao^*; Zhang, Xue; Huang, Feng; Yang, Bin; Li, Jun; Liu, Bingfeng; Luo, Haihua; Zhang, Ping; Zhang, Hui

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(35): 29373-29383.

DOI：10.1074/jbc.M112.354001

• MESSENGER-RNA DEGRADATION
• REVERSE TRANSCRIPTION
• PROTEIN-SYNTHESIS
• STRESS GRANULES
• 7SL RNA
• DROSOPHILA
• GW182
• BIOGENESIS
• COMPLEXES
• FAMILY

The apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) is a potent restrictive factor for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. It belongs to the cytidine deaminase family. Recent studies have shown that A3G significantly inhibits microRNA (miRNA)-mediated repression of translation. However, the mechanism underlying this action must be clarified. In this report, we have demonstrated that A3G counteracts miRNA-mediated repression of translation by inhibiting the interaction between moloney leukemia virus 10 (MOV10) protein and Argonaute-2 (AGO2), causing either abnormal assembly or abnormal maturation of miRNA-inducing silencing complex (miRISC). Through a series of MOV10 deletions, we found that A3G binds to a domain at the C terminus in MOV10, where it competitively inhibits the binding of AGO2 to that same domain. The interaction between A3G and MOV10 relies on its association with a small RNA named 7SL RNA. The A3G mutant W127L, which is unable to bind to 7SL RNA, shows significantly incapability to counteract the miRNA-mediated repression of translation. Our data demonstrate a novel mechanism involved in the regulation of miRISC activity. Although both A3G and MOV10 belong to the interferon antiviral system and inhibit HIV-1 and other retroviruses, their opposing effects on the cellular miRNA activity suggest that they play much more complicated regulatory roles in various cellular functions.

• 出版日期2012-8-24
• 单位中山大学