Residues that affect human Argonaute2 concentration in cytoplasmic processing bodies.
Sequence-specific gene silencing triggered by double-stranded RNA is a fundamental gene regulatory mechanism present in almost all eukaryotes. Argonaute2 (Ago2) is the central protein component of RNA-induced silencing complex (RISC), and resides in cytoplasmic processing bodies (P-bodies). In the present study, we demonstrated one human mutant Ago2 protein containing 6 point mutations (G32W, F128L, R196Q, P458S, T741A, S752G) failed to accumulate in P-bodies. Analysis of the different Ago2 revertants indicates the S752 as a key amino acid for P-body localization of Ago2. The S752 is evolutionary conserved in the Piwi domain of Ago2 homologs from worms, insects, plants and mammals. We further showed the single point mutation S752G interfering the interaction between Ago2 and Dcp1a, a key component of P-bodies.
Zhou
Huamin
H
The Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, 422 South Siming Road, Xiamen, Fujian 361005, China.
Yang
Lin
L
Li
Hanjie
H
Li
Linjie
L
Chen
Jianming
J
D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D003593:Cytoplasm / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D034743:RNA-Induced Silencing Complex; D015534:Trans-Activators; D004722:Endoribonucleases; C466279:DCP1A protein, human