第2期 周冰涵,严小璇,蓝文贤,等:胞嘧啶脱氨基酶 APOBECI研究进展 目的是啮齿动物和兔源 APOBEC1具有不受Ⅴif影响的抗HIV-1活性,其中兔源 APOBECI能够高效地掺 入病毒粒子并直接编辑病毒基因组,但脱氨基活性位点Glu63的突变并不能完全消除兔源 APOBECI的 HIV-1抑制作用,说明兔源 APOBECI还以一种较弱的,不同于脱氨基催化的机制抵抗HV-1,阐明这种 机制有助于加深对 APObeC家族抗病毒功能的理解 参考文献: 1] HARRIS R S, LIDDAMENT M T Retroviral restriction by APOBEC proteins [J]. Nature Reviews Immunology, 2004,4 (11):868-877. [ 2] SWANTON C, MCGRANAHAN N. STARRETT G J, et al. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity [J]. Cancer Discovery, 2015.5(7):704-712 3] SNYDER E M, MCCARTY C, MEHALOW A, et al. APOBECI complementation factor(AlCF)is dispensable for C-to-U RNA editing in vivo [J].RNA(New York, N.Y.), 2017, 23(4): 457-465. [4] FOSSAT N, TOURLE K, RADZIEWIC T, et al. C to U RNA editing mediated by APOBECI requires RNA-binding protein RBM47[J] EMBO Reports,2014,15(8):903-910 [5] IKEDA T, ONG E B B WATANABE N, et al. Creation of chimeric human/rabbit APOBECI with HIV-I restriction and DNA mutation activities [J]. Scientific Reports, 2016, 6: 19035 6 YAMANAKA S, POKSAY K S, BALESTRA M E, et al. Cloning and mutagenesis of the rabbit ApoB mRNA editing protein: a zine motif is essential for catalytic activity, and noncatalytic auxiliary factor()of the editing complex are widely distributed [J]. The Journal of Biological Chemistry, 1994, 269(34): 21725-21734 [7] ROBBINS J, DILWORTH S M, LASKEY R A, et al.Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence [J].Cell, 1991, 64(3): 615-623 [8] TENG B B, OCHSNER S, ZHANG Q et al. Mutational analysis of apolipoprotein B mRNA editing enzyme(APOBEC1) structure-function relationships of RNA editing and dimerization [J]Journal of Lipid Research. 1999. 40(4): 623-635 [9] MEHTA A. BANERJEE S, DRISCOLL D M. APOBECI interacts with a 65 k Da complementing protein to edit apolipoprotein-B mRNA in vitro [J]. The Journal of Biological Chemistry. 1996.271(45): 28294-28299 10] LAU PP,, ZHU H J. BALDINI A, et al. Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene [J]. Proceedings of the National Academy of Sciences, 1994. 91(18):8522 [11] OKA K, KOBAYASHI K, SULLIVAN M, et al. Tissue-specific inhibition of apolipoprotein B mRNA editing in the liver by adenovirus-mediated transfer of a dominant negative mutant APOBECI leads to increased low density lipoprotein in mice [J]. The Journal of Biological Chemistry, 1997, 272(3):1456-1460 [12] HARRIS R S, PETERSEN-MAHRTS K, NEUBERGER M S RNA editing enzyme APOBECI and some of its homologs can act as DNA mutators []. Molecular Cell, 2002, 10(5): 1247-1253 13] XIE K, SOWDEN M P, DANCE G S C, et al. The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBECI [J]. Proceedings of the National Academy of Sciences 2004,101(21):8114-811 [14] NAVARATNAM N, BHATTACHARYA S, FUJINO T, et al. Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site[J].Cell, 1995, 81(2): 187-195 [15 NAVARATNAM N, FUJINO T, BAYLISS J, et al.Escherich ApoB RNA editing and a mechanism for RNA substrate recognition [J]. Jourmal of Molecular Biology, 1998. 275(4) 16] TENG B, BURANT C F, DAVIDSON N O Molecular cloning of an apolipoprotein B messenger RNA editing protein [J]第2期 周冰涵，严小璇，蓝文贤，等：胞嘧啶脱氨基酶APOBEC1研究进展 目的是啮齿动物和兔源APOBEC1具有不受Vif影响的抗HIV-1活性，其中兔源APOBEC1能够高效地掺 入病毒粒子并直接编辑病毒基因组，但脱氨基活性位点Glu63的突变并不能完全消除兔源APOBEC1的 HIV-1抑制作用，说明兔源 APOBEC1还以一种较弱的，不同于脱氨基催化的机制抵抗 HIV-1，阐明这种 机制有助于加深对APOBEC家族抗病毒功能的理解. 参考文献： ［1］ HARRIS R S，LIDDAMENT M T.Retroviral restriction by APOBEC proteins［J］.Nature Reviews Immunology，2004，4 （11）：868－877. ［2］ SWANTON C，MCGRANAHAN N，STARRETT G J，et al.APOBEC enzymes：mutagenic fuel for cancer evolution and heterogeneity［J］.Cancer Discovery，2015，5（7）：704－712. ［3］ SNYDER E M，MCCARTY C，MEHALOW A，et al.APOBEC1 complementation factor（A1CF）is dispensable for C-to-U RNA editing in vivo［J］.RNA（New York，N.Y.），2017，23（4）：457－465. ［4］ FOSSAT N，TOURLE K，RADZIEWIC T，et al.C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47［J］.EMBO Reports，2014，15（8）：903－910. ［5］ IKEDA T，ONG E B B，WATANABE N，et al.Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities［J］.Scientific Reports，2016，6：19035. ［6］ YAMANAKA S，POKSAY K S，BALESTRA M E，et al. Cloning and mutagenesis of the rabbit ApoB mRNA editing protein：a zinc motif is essential for catalytic activity，and noncatalytic auxiliary factor（s）of the editing complex are widely distributed［J］.The Journal of Biological Chemistry，1994，269（34）：21725－21734. ［7］ ROBBINS J，DILWORTH S M，LASKEY R A，et al.Two interdependent basic domains in nucleoplasmin nuclear targeting sequence：identification of a class of bipartite nuclear targeting sequence［J］.Cell，1991，64（3）：615－623. ［8］ TENG B B，OCHSNER S，ZHANG Q，et al.Mutational analysis of apolipoprotein B mRNA editing enzyme（APOBEC1）： structure-function relationships of RNA editing and dimerization［J］.Journal of Lipid Research，1999，40（4）：623－635. ［9］ MEHTA A，BANERJEE S，DRISCOLL D M. APOBEC1 interacts with a 65 kDa complementing protein to edit apolipoprotein-B mRNA in vitro［J］.The Journal of Biological Chemistry，1996，271（45）：28294－28299. ［10］ LAU P P，ZHU H J，BALDINI A，et al.Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene［J］.Proceedings of the National Academy of Sciences，1994，91（18）：8522－ 8526. ［11］ OKA K，KOBAYASHI K，SULLIVAN M，et al.Tissue-specific inhibition of apolipoprotein B mRNA editing in the liver by adenovirus-mediated transfer of a dominant negative mutant APOBEC1 leads to increased low density lipoprotein in mice ［J］.The Journal of Biological Chemistry，1997，272（3）：1456－1460. ［12］ HARRIS R S，PETERSEN-MAHRT S K，NEUBERGER M S.RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators［J］.Molecular Cell，2002，10（5）：1247－1253. ［13］ XIE K，SOWDEN M P，DANCE G S C，et al.The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC1［J］. Proceedings of the National Academy of Sciences， 2004，101（21）：8114－8119. ［14］ NAVARATNAM N，BHATTACHARYA S，FUJINO T，et al.Evolutionary origins of apoB mRNA editing：catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site［J］.Cell，1995，81（2）：187－195. ［15］ NAVARATNAM N，FUJINO T，BAYLISS J，et al.Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognition［J］.Journal of Molecular Biology，1998，275（4）： 695－714. ［16］ TENG B，BURANT C F，DAVIDSON N O.Molecular cloning of an apolipoprotein B messenger RNA editing protein［J］. 241