APOBEC3G inhibits microRNA-mediated repression of translation by interfering with the interaction between Argonaute-2 and MOV10.
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.
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. chaoliulc@yahoo.com.cn
Chao
C
Liu
Xue
X
Zhang
Feng
F
Huang
Bin
B
Yang
Jun
J
Li
Bingfeng
B
Liu
Haihua
H
Luo
Ping
P
Zhang
Hui
H
Zhang
D000071480:APOBEC-3G Deaminase; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D020733:RNA, Small Cytoplasmic / Q000235:genetics / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000235:genetics / Q000378:metabolism*
C115990:7SL RNA; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D020733:RNA, Small Cytoplasmic; D018271:Signal Recognition Particle; C530476:Mov10 protein, human; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D020365:RNA Helicases