Dicer的结构功能及其与肿瘤的关系
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摘要
Dicer蛋白是RNaseⅢ家族中重要的一员,对miRNA或siRNA的产生起着至关重要的作用。Dicer蛋白通常由1个DEXH盒子或H盒子、1个DUF283结构域、1个PAZ结构域、2个RNaseⅢ结构域(RNaseⅢa和RNaseⅢb)和1个dsRNA结合结构域组成。Dicer蛋白的分子结构决定了其在miRNAs合成中发挥着重要作用。Dicer及生成的miRNA与肿瘤又有着密切关系。本文主要针对Dicer及其与肿瘤的关系作简要综述。
Dicer protein is one of the members of the RNaseⅢ family. Dicer is responsible for producing microRNA and small interfering RNA. Dicer comprises a DEx D / H-box helicase,a DUF283 domain,a PAZ domain,two RNase Ⅲ domains( RNase Ⅲ a and RNase Ⅲ b) and a dsRNA-binding domain( dsRBD). The role of Dicer in the synthesis of miRNAs is determined by its protein structure. In addition,Dicer protein and its generated miRNA are closely involved in tumor. This review aimed to provide an overview for the structure and function of Dicer and its role in tumor.
Dicer protein is one of the members of the RNaseⅢ family. Dicer is responsible for producing microRNA and small interfering RNA. Dicer comprises a DEx D / H-box helicase,a DUF283 domain,a PAZ domain,two RNase Ⅲ domains( RNase Ⅲ a and RNase Ⅲ b) and a dsRNA-binding domain( dsRBD). The role of Dicer in the synthesis of miRNAs is determined by its protein structure. In addition,Dicer protein and its generated miRNA are closely involved in tumor. This review aimed to provide an overview for the structure and function of Dicer and its role in tumor.
引文
[1]Kim V N,Han J,Siomi M C.Biogenesis of small RNAs in animals[J]Nat Rev Mol Cell Biol,2009,10(2):126-139
[2]Meister G,Tuschl T.Mechanisms of gene silencing by doublestranded RNA[J].Nature,2004,431(7006):343-349
[3]Saito K,Siomi M C.Small RNA-mediated quiescence of transposable elements in animals[J].Dev Cell,2010,19(5):687-697
[4]MacRae I J,Doudna J A.Ribonuclease revisited:structural insights into ribonuclease III family enzymes[J].Curr Opin Struct Biol,2007,17(1):138-145
[5]Jinek M,Doudna J A.A three-dimensional view of the molecular machinery of RNA interference[J].Nature,2009,457(7228):405-412
[6]Cheloufi S,Dos Santos C O,Chong M M,et al.A dicerindependent miRNA biogenesis pathway that requires Ago catalysis[J].Nature,2010,465(7298):584-589
[7]Bernstein E,Kim SY,Carmell MA,et al.Dicer is essential for mouse development[J].Nat Genet,2003,35(3):215-217
[8]Devasthanam A S,Tomasi T B.Dicer in immune cell development and function[J].Immunol Invest,2013,43(2):182-195
[9]Mori M A,Prashant R,Thomas T,et al.Role of microRNA processing in adipose tissue in stress defense and longevity[J].Cell Metab,2012,16(3):336-347
[10]Kaneko H,Dridi S,Tarallo V,et al.DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration[J].Nature,2011,471(7338):325-330
[11]Foulkes WD,Priest JR,Duchaine TF.DICER1:mutations,microRNAs and mechanisms[J].Nat Rev Cancer,2014,14(10):662-672
[12]Zhang H,Kolb F A,Jaskiewicz L,et al.Single processing center models for human Dicer and bacterial RNase III[J].Cell,2004,118(1):57-68
[13]Dlakic'M.DUF283 domain of Dicer proteins has a doublestranded RNA-binding fold[J].Bioinformatics,2006,22(22):2711-2714
[14]Collins RE,Cheng X.Structural domains in RNAi[J].FEBS Lett,2005,579(26):5841-5849
[15]MacRae IJ,Zhou K,Li F,et al.Structural basis for doublestranded RNA processing by Dicer[J].Science,2006,311(5758):195-198
[16]Blaszczyk J,Tropea JE,Bubunenko M,et al.Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage[J].Structure,2001,9(12):1225-1236
[17]Fujioka Y,Utsumi M,Ohba Y,et al.Location of a possible miRNA processing site in Sm D3/Sm B nuclear bodies in Arabidopsis[J].Plant Cell Physiol,2007,48(9):1243-1253
[18]Moissiard G,Parizotto EA,Himber C,et al.Transitivity in Arabidopsis can be primed,requires the redundant action of the antiviral Dicer-like 4 and Dicer-like 2,and is compromised by viral-encoded suppressor proteins[J].RNA,2007,13(8):1268-1278
[19]Gasciolli V,Mallory AC,Bartel DP,et al.Partially redundant functions of Arabidopsis DICER-like enzymes and a role for DCL4in producing trans-acting siRNAs[J].Curr Biol,2005,915(16):1494-1500
[20]Pikaard CS.Cell biology of the Arabidopsis nuclear siRNA pathway for RNA-directed chromatin modification[J].Cold Spring Harb Symp Quant Biol,2006,71:473-480
[21]Deleris A,Gallegobartolome J,Bao J,et al.Hierarchical action and inhibition of plant Dicer-like proteins in antiviral defense[J].Science,2006,313(5783):68-71
[22]Liu X,Park J K,Jiang F,et al.Dicer-1,but not Loquacious,is critical for assembly of miRNA-induced silencing complexes[J].RNA,2007,13(12):2324-2329
[23]Kagami M,Sekita Y,Nishimura G,et al.Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes[J].Nat Genet,2008,40(2):237-242
[24]Jin Z,Xie T.Dcr-1 maintains Drosophila ovarian stem cells[J].Curr Biol,2007,17(6):539-544
[25]Filipowicz W,Jaskiewicz L,Kolb F A,et al.Posttranscriptional gene silencing by siRNAs and miRNAs[J].Curr Opin Struct Biol,2005,15(3):331-341
[26]Hutvagner G,Simard M J.Argonaute proteins:key players in RNA silencing[J].Nat Rev Mol Cell Biol,2008,9(9):22-32
[27]Wei K F,Wu L J,Chen J,et al.Structural evolution and functional diversification analyses of argonaute protein[J].J Cellular Biochem,2012,113(8):2576-2585
[28]Wei K,Wu L,Chen Y,et al.Argonaute protein as a linker to command center of physiological processes[J].Chin J Cancer Res,2013,25(4):430-441
[29]Provost P,Dishart D,Doucet J,et al.Ribonuclease activity and RNA binding of recombinant human Dicer[J].EMBO J,2002,21(21):5864-5874
[30]Park J E,Heo I,Tian Y,et al.Dicer recognizes the 5'end of RNA for efficient and accurate processing[J].Nature,2011,475(7355):201-205
[31]Lee HY,Zhou K,Smith AM,et al.Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing[J].Nucleic Acids Res,2013,41(13):6568-6576
[32]谢兆辉,李学贵,许禔森.miRNA的异构体——isomiR[J].中国生物化学与分子生物学报(Xie ZH,Li XG,Xu TS.The isoforms of miRNA—isomiR[J].Chin J Biochem Mol Biol),2014,30(8):739-745
[33]Ma H,Wu Y,Niu Q,et al.A sliding-bulge structure at the Dicer processing site of pre-miRNAs regulates alternative Dicer processing to generate 5'-isomiRs[J].Heliyon,2016,2(9):e00148
[34]Humphreys DT,Hynes CJ,Patel HR,et al.Complexity of murine cardiomyocyte miRNA biogenesis,sequence variant expression and function[J].Plo S One,2012,7(2):57-57
[35]Roberts T C.The microRNA Machinery,In:microRNA:Basic Science[M].Springer International Publishing,2015:15-30
[36]Kim Y K,Kim B,Kim V N.Re-evaluation of the roles of DROSHA,Exportin 5,and DICER in microRNA biogenesis[J].Proc Natl Acad Sci U S A,2016,113(13):E1881-E1889
[37]Galiana-Arnoux D,Dostert C,Schneemann A,et al.Essential function in vivo for Dicer-2 in host defense against RNA viruses in Drosophila[J].Nat Immunol,2006,7(6):590-597
[38]Heravi-Moussavi A,Anglesio M S,Cheng S W,et al.Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers[J].N Engl J Med,2012,366(3):234-242
[39]Wu MK,Sabbaghian N,Xu B,et al.Biallelic DICER1mutations occur in Wilms tumours[J].J Pathol,2013,230(2):154-164
[40]Bahubeshi A,Tischkowitz M,Foulkes WD.miRNA processing and human cancer:DICER1 cuts the mustard[J].Sci Transl Med,2011,3(111):111ps4
[41]Anglesio M S,Wang Y,Yang W,et al.Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage[J].J Pathol,2013,229(3):400-409
[42]Slade I,Bacchelli C,Davies H,et al.DICER1 syndrome:clarifying the diagnosis,clinical features and management implications of a pleiotropic tumour predisposition syndrome[J].J Med Genet,2011,48(4):273-278
[43]Chiosea S,Jelezcova E,Chandran U,et al.Overexpression of Dicer in precursor lesions of lung adenocarcinoma[J].Cancer Res,2007,67(5):2345-2350
[44]Kurzynskakokorniak A,Koralewska N,Pokornowska M,et al.The many faces of Dicer:the complexity of the mechanisms regulating Dicer gene expression and enzyme activities[J].Nucleic Acids Res,2015,43(9):4365-4380
[45]Ma Z,Swede H,Cassarino D,et al.Up-regulated Dicer expression in patients with cutaneous melanoma[J].Plo S One,2011,6(6):e20494
[46]Jafarnejad S M,Ardekani G S,Ghaffari M,et al.Sox4-mediated Dicer expression is critical for suppression of melanoma cell invasion[J].Oncogene,2013,32(17):2131-2139
[47]Sand M,Skrygan M,Georgas D,et al.The miRNA machinery in primary cutaneous malignant melanoma,cutaneous malignant melanoma metastases and benign melanocytic nevi[J].Cell Tissue Res,2012,350(1):119-126
[48]Hoffend N C,Magner W J,Tomasi T B.The modulation of Dicer regulates tumor immunogenicity in melanoma[J].Oncotarget,2016,7(30):47663-47673
[49]Kumar M S,Pester R E,Chen C Y,et al.Dicer1 functions as a haploinsufficient tumor suppressor[J].Genes Dev,2009,23(23):2700-2704
[50]Knudson A G Jr.Mutation and cancer:statistical study of retinoblastoma[J].Proc Natl Acad Sci U S A,1971,68(4):820-823
[51]Sahakitrungruang T,Srichomthong C,Pornkunwilai S,et al.Germline and somatic DICER1 mutations in a pituitary blastoma causing infantile-onset Cushings disease[J].J Clin Endocrinol Metab,2014,99(8):E1487-1492
[52]Wiesen J L,Tomasi T B.Dicer is regulated by cellular stresses and interferons[J].Mol Immunol,2009,46(6):1222-1228
[53]Zhu Y,Cai L,Guo J,et al.Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3expression[J].Tumor Biol,2016,37:14009-14023
[2]Meister G,Tuschl T.Mechanisms of gene silencing by doublestranded RNA[J].Nature,2004,431(7006):343-349
[3]Saito K,Siomi M C.Small RNA-mediated quiescence of transposable elements in animals[J].Dev Cell,2010,19(5):687-697
[4]MacRae I J,Doudna J A.Ribonuclease revisited:structural insights into ribonuclease III family enzymes[J].Curr Opin Struct Biol,2007,17(1):138-145
[5]Jinek M,Doudna J A.A three-dimensional view of the molecular machinery of RNA interference[J].Nature,2009,457(7228):405-412
[6]Cheloufi S,Dos Santos C O,Chong M M,et al.A dicerindependent miRNA biogenesis pathway that requires Ago catalysis[J].Nature,2010,465(7298):584-589
[7]Bernstein E,Kim SY,Carmell MA,et al.Dicer is essential for mouse development[J].Nat Genet,2003,35(3):215-217
[8]Devasthanam A S,Tomasi T B.Dicer in immune cell development and function[J].Immunol Invest,2013,43(2):182-195
[9]Mori M A,Prashant R,Thomas T,et al.Role of microRNA processing in adipose tissue in stress defense and longevity[J].Cell Metab,2012,16(3):336-347
[10]Kaneko H,Dridi S,Tarallo V,et al.DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration[J].Nature,2011,471(7338):325-330
[11]Foulkes WD,Priest JR,Duchaine TF.DICER1:mutations,microRNAs and mechanisms[J].Nat Rev Cancer,2014,14(10):662-672
[12]Zhang H,Kolb F A,Jaskiewicz L,et al.Single processing center models for human Dicer and bacterial RNase III[J].Cell,2004,118(1):57-68
[13]Dlakic'M.DUF283 domain of Dicer proteins has a doublestranded RNA-binding fold[J].Bioinformatics,2006,22(22):2711-2714
[14]Collins RE,Cheng X.Structural domains in RNAi[J].FEBS Lett,2005,579(26):5841-5849
[15]MacRae IJ,Zhou K,Li F,et al.Structural basis for doublestranded RNA processing by Dicer[J].Science,2006,311(5758):195-198
[16]Blaszczyk J,Tropea JE,Bubunenko M,et al.Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage[J].Structure,2001,9(12):1225-1236
[17]Fujioka Y,Utsumi M,Ohba Y,et al.Location of a possible miRNA processing site in Sm D3/Sm B nuclear bodies in Arabidopsis[J].Plant Cell Physiol,2007,48(9):1243-1253
[18]Moissiard G,Parizotto EA,Himber C,et al.Transitivity in Arabidopsis can be primed,requires the redundant action of the antiviral Dicer-like 4 and Dicer-like 2,and is compromised by viral-encoded suppressor proteins[J].RNA,2007,13(8):1268-1278
[19]Gasciolli V,Mallory AC,Bartel DP,et al.Partially redundant functions of Arabidopsis DICER-like enzymes and a role for DCL4in producing trans-acting siRNAs[J].Curr Biol,2005,915(16):1494-1500
[20]Pikaard CS.Cell biology of the Arabidopsis nuclear siRNA pathway for RNA-directed chromatin modification[J].Cold Spring Harb Symp Quant Biol,2006,71:473-480
[21]Deleris A,Gallegobartolome J,Bao J,et al.Hierarchical action and inhibition of plant Dicer-like proteins in antiviral defense[J].Science,2006,313(5783):68-71
[22]Liu X,Park J K,Jiang F,et al.Dicer-1,but not Loquacious,is critical for assembly of miRNA-induced silencing complexes[J].RNA,2007,13(12):2324-2329
[23]Kagami M,Sekita Y,Nishimura G,et al.Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes[J].Nat Genet,2008,40(2):237-242
[24]Jin Z,Xie T.Dcr-1 maintains Drosophila ovarian stem cells[J].Curr Biol,2007,17(6):539-544
[25]Filipowicz W,Jaskiewicz L,Kolb F A,et al.Posttranscriptional gene silencing by siRNAs and miRNAs[J].Curr Opin Struct Biol,2005,15(3):331-341
[26]Hutvagner G,Simard M J.Argonaute proteins:key players in RNA silencing[J].Nat Rev Mol Cell Biol,2008,9(9):22-32
[27]Wei K F,Wu L J,Chen J,et al.Structural evolution and functional diversification analyses of argonaute protein[J].J Cellular Biochem,2012,113(8):2576-2585
[28]Wei K,Wu L,Chen Y,et al.Argonaute protein as a linker to command center of physiological processes[J].Chin J Cancer Res,2013,25(4):430-441
[29]Provost P,Dishart D,Doucet J,et al.Ribonuclease activity and RNA binding of recombinant human Dicer[J].EMBO J,2002,21(21):5864-5874
[30]Park J E,Heo I,Tian Y,et al.Dicer recognizes the 5'end of RNA for efficient and accurate processing[J].Nature,2011,475(7355):201-205
[31]Lee HY,Zhou K,Smith AM,et al.Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing[J].Nucleic Acids Res,2013,41(13):6568-6576
[32]谢兆辉,李学贵,许禔森.miRNA的异构体——isomiR[J].中国生物化学与分子生物学报(Xie ZH,Li XG,Xu TS.The isoforms of miRNA—isomiR[J].Chin J Biochem Mol Biol),2014,30(8):739-745
[33]Ma H,Wu Y,Niu Q,et al.A sliding-bulge structure at the Dicer processing site of pre-miRNAs regulates alternative Dicer processing to generate 5'-isomiRs[J].Heliyon,2016,2(9):e00148
[34]Humphreys DT,Hynes CJ,Patel HR,et al.Complexity of murine cardiomyocyte miRNA biogenesis,sequence variant expression and function[J].Plo S One,2012,7(2):57-57
[35]Roberts T C.The microRNA Machinery,In:microRNA:Basic Science[M].Springer International Publishing,2015:15-30
[36]Kim Y K,Kim B,Kim V N.Re-evaluation of the roles of DROSHA,Exportin 5,and DICER in microRNA biogenesis[J].Proc Natl Acad Sci U S A,2016,113(13):E1881-E1889
[37]Galiana-Arnoux D,Dostert C,Schneemann A,et al.Essential function in vivo for Dicer-2 in host defense against RNA viruses in Drosophila[J].Nat Immunol,2006,7(6):590-597
[38]Heravi-Moussavi A,Anglesio M S,Cheng S W,et al.Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers[J].N Engl J Med,2012,366(3):234-242
[39]Wu MK,Sabbaghian N,Xu B,et al.Biallelic DICER1mutations occur in Wilms tumours[J].J Pathol,2013,230(2):154-164
[40]Bahubeshi A,Tischkowitz M,Foulkes WD.miRNA processing and human cancer:DICER1 cuts the mustard[J].Sci Transl Med,2011,3(111):111ps4
[41]Anglesio M S,Wang Y,Yang W,et al.Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage[J].J Pathol,2013,229(3):400-409
[42]Slade I,Bacchelli C,Davies H,et al.DICER1 syndrome:clarifying the diagnosis,clinical features and management implications of a pleiotropic tumour predisposition syndrome[J].J Med Genet,2011,48(4):273-278
[43]Chiosea S,Jelezcova E,Chandran U,et al.Overexpression of Dicer in precursor lesions of lung adenocarcinoma[J].Cancer Res,2007,67(5):2345-2350
[44]Kurzynskakokorniak A,Koralewska N,Pokornowska M,et al.The many faces of Dicer:the complexity of the mechanisms regulating Dicer gene expression and enzyme activities[J].Nucleic Acids Res,2015,43(9):4365-4380
[45]Ma Z,Swede H,Cassarino D,et al.Up-regulated Dicer expression in patients with cutaneous melanoma[J].Plo S One,2011,6(6):e20494
[46]Jafarnejad S M,Ardekani G S,Ghaffari M,et al.Sox4-mediated Dicer expression is critical for suppression of melanoma cell invasion[J].Oncogene,2013,32(17):2131-2139
[47]Sand M,Skrygan M,Georgas D,et al.The miRNA machinery in primary cutaneous malignant melanoma,cutaneous malignant melanoma metastases and benign melanocytic nevi[J].Cell Tissue Res,2012,350(1):119-126
[48]Hoffend N C,Magner W J,Tomasi T B.The modulation of Dicer regulates tumor immunogenicity in melanoma[J].Oncotarget,2016,7(30):47663-47673
[49]Kumar M S,Pester R E,Chen C Y,et al.Dicer1 functions as a haploinsufficient tumor suppressor[J].Genes Dev,2009,23(23):2700-2704
[50]Knudson A G Jr.Mutation and cancer:statistical study of retinoblastoma[J].Proc Natl Acad Sci U S A,1971,68(4):820-823
[51]Sahakitrungruang T,Srichomthong C,Pornkunwilai S,et al.Germline and somatic DICER1 mutations in a pituitary blastoma causing infantile-onset Cushings disease[J].J Clin Endocrinol Metab,2014,99(8):E1487-1492
[52]Wiesen J L,Tomasi T B.Dicer is regulated by cellular stresses and interferons[J].Mol Immunol,2009,46(6):1222-1228
[53]Zhu Y,Cai L,Guo J,et al.Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3expression[J].Tumor Biol,2016,37:14009-14023