RNA修复研究进展
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摘要
机体DNA损伤修复的机制目前已研究得比较全面,而RNA损伤修复的研究却没有引起广泛的认识.主要由于人们长期以来认为损伤的RNA会被机体特异性降解而不是修复.近年来,随着多个RNA损伤修复系统的相继发现,揭示机体对损伤RNA可能优先选择进行修复.本文从噬菌体型RNA修复系统、细菌型RNA修复系统、酵母型RNA修复系统和人类的RNA损伤修复系统四个方面对目前RNA损伤修复研究的最新进展做一综述.
The mechanism of the organism to repair DNA damage has been studied in reasonable detail.In contrast,the agents of damage to DNA also cause RNA damage have not been widely recognized.This is mainly due to aberrant RNAs are generally assumed to be degraded rather than repaired.With the discovery of RNA repair systems,the RNA damage of the organism may preferentially be repaired.Based on the latest findings,the phage-type RNA repair system,bacterial-type RNA repair system,yeast-type RNA repair system and human RNA damage repair system are reviewed and discussed in this paper.
The mechanism of the organism to repair DNA damage has been studied in reasonable detail.In contrast,the agents of damage to DNA also cause RNA damage have not been widely recognized.This is mainly due to aberrant RNAs are generally assumed to be degraded rather than repaired.With the discovery of RNA repair systems,the RNA damage of the organism may preferentially be repaired.Based on the latest findings,the phage-type RNA repair system,bacterial-type RNA repair system,yeast-type RNA repair system and human RNA damage repair system are reviewed and discussed in this paper.
引文
[1]Aas P A,Otterlei M,Falnes P O,et al.Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA.Nature,2003,421(6925):859-863
[2]Chan C M,Zhou C,Huang R H.Reconstituting bacterial RNA repair and modification in vitro.Science,2009,326(5950):247
[3]Amitsur M,Levitz R,Kaufman G.Bacteriophage T4 anticodon nuclease,polynucleotide kinase,and RNA ligase reprocess the host lysine tRNA.EMBOJ,1987,6(8):2499-2503
[4]Klaiman D,Kaufmann G.Phage T4-induced dTTP accretion bolsters a tRNase-based host defense.Virology,2011,414(1):97-101
[5]Abelson J,Trotta C R,Li H.tRNA splicing.J Biol Chem,1998,273(21):12685-12688
[6]Sidrauski C,Cox J S,Walter P.tRNA ligase is required for regulated mRNA splicing in the unfolded protein response.Cell,1996,87(3):405-413
[7]Wang L K,Lima C D,Shuman S.Structure and mechanism of T4polynucleotide kinase:an RNA repair enzyme.EMBOJ,2002,21(14):3873-3880
[8]Das U,Shuman S.Mechanism of RNA 2忆,3忆-cyclic phosphate end healing by T4 polynucleotide kinase-phosphatase.Nucleic Acids Res,2013,41(1):355-365
[9]Jayakrishnan N,Beate S,Raffael S,et al.RNA repair:an antidote to cytotoxic eukaryal RNA damage.Mol Cell,2008,31(2):278-286
[10]Cranston J W,Silber R,Malathi V G,et al.Studies on ribonucleic acid ligase:characterization of an adenosine triphosphate-inorganic pyrophosphate exchange reaction and demonstration of an enzyme-adenylate complex with T4 bacteriophage-induced enzyme.J Biol Chem,1974,249(23):7447-7456
[11]Sugino A,Snoper T J,Cozzarelli N R.Bacteriophage T4 RNA ligase.Reaction intermediates and interaction of substrates.J Biol Chem,1977,252(5):1732-1738
[12]Martins A,Shuman S.An end-healing enzyme from Clostridium thermocellum with 5忆kinase,2忆,3忆phosphatese,and adenylyltransferase activities.RNA,2005,11(8):1271-1280
[13]Wang L K,Das U,Smith P,et al.Structure and mechanism of the polynucleotide kinase component of the bacterial Pnkp-Hen1 RNA repair system.RNA,2012,18(12):2277-2286
[14]Paul S,Li Kai W,Pravin A,et al.The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family.Proc Natl Acad Sci USA,2012,109(7):2296-2301
[15]Wang P,Chan C M,Christensen D,et al.Molecular basis of bacterial protein Hen1 activating the ligase activity of bacterial protein Pnkp for RNA repair.Proc Natl Acad Sci USA,2012,109(33):13248-13253
[16]Yu B,Yang Z,Li J,et al.Methylation as a crucial step in plant microRNA biogenesis.Science,2005,307(5711):932-935
[17]Saito K,Sakaguchi Y,Suzuki T,et al.Pimet,the Drosophila homolog of HEN1,mediates 2忆-O-methylation of Piwi-interacting RNAs at their 3忆ends.Genes Dev,2007,21(13):1603-1608
[18]Kamminga L M,Luteijn M J,den Broeder M J,et al.Hen1 is required for oocyte development and piRNA stability in zebrafish.EMBOJ,2010,29(21):3688-3700
[19]Kirino Y,Mourelatos Z.Mouse Piwi-interacting RNAs are 2忆-Omethylated at their 3忆termini.Nat Struct Mol Biol,2007,14(4):347-348
[20]Jain R,Shuman S.Bacterial Hen1 is a 3忆terminal RNA ribose 2忆O-methyltransferase component of a bacterial RNA repair cassette.RNA,2010,16(2):316-323
[21]Jain R,Shuman S.Active site mapping and substrate specificity of bacterial Hen1,a manganese-dependent 3忆-terminal RNA ribose 2忆-O-methyltransferase.RNA,2011,17(3):429-438
[22]Mui Chan C,Zhou C,Brunzelle J S,et al.Structural and biochemical insights into 2忆-O-methylation at the 3忆-terminal nucleotide of RNA by Hen1.Proc Natl Acad Sci USA,2009,106(42):17699-17704
[23]Huang R H.Unique 2忆-O-methylation by Hen1 in eukaryotic RNA interference and bacterial RNA repair.Biochemistry,2012,51(20):4087-4095
[24]Wang L K,Shuman S.Structure-function analysis of yeast tRNA ligase.RNA,2005,11(6):966-975
[25]Sawaya R,Schwer B,Shuman S.Genetic and biochemical analysis of the functional domains of yeast tRNA ligase.J Biol Chem,2003,278(45):43928-43938
[26]Spinelli S L,Consaul S A,Phizicky E M.A conditional lethal yeast phosphotransferase mutant accumulates tRNA with a 2忆-phosphate and an unmodified base at the splice junction.RNA,1997,3(12):1388-1400
[27]Englert M,Beier H.Plant tRNA ligases are multifunctional enzymes that have diverged in sequence and substrate specificity from RNA ligases of other phylogenetic origins.Nucleic Acids Res,2005,33(1):388-399
[28]Wang L K,Schwer B,Englert M,et al.Structure-function analysis of the kinase-CPD domain of yeast tRNA ligase(Trl1)and requirements for complementation of tRNA splicing by a plant Trl1homolog.Nucleic Acids Res,2006,34(2):517-527
[29]Yang C G,Yi C,Duguid E M,et al.Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA.Nature,2008,452(7190):961-966
[30]Aravind L,Koonin E V.The DNA-repair protein AlkB,EGL-9,and leprecan define new families of 2-oxoglu-tarate-and irondependent dioxygenases.Genome Biol,2001,2(3):research0007.1-research0007.8
[31]Falnes P O,Johansen R F,Seeberg E.AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli.Nature,2002,419(6903):178-182
[32]Trewick S C,Henshaw T F,Hausinger R P,et al.Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage.Nature,2002,419(6903):174-178
[33]Ougland R,Zhang C M,Liiv A,et al.AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation.Mol Cell,2004,16(1):107-116
[34]VgbφC B,Svaasand E K,Aas P A,et al.Methylation damage to RNA induced in vivo in Escherichia coli is repaired by endogenous AlkB as part of the adaptive response.DNA Repair(Amst),2013,12(3):188-195
[35]Sundhein O,VgbφC B,Bjφrs M,et al.Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.EMBO J,2006,25(14):3389-3397
[36]Yi C,Yang C G,He C.A non-heme iron-mediated chemical demethylation in DNA and RNA.Acc Chem Res,2009,42(4):519-529
[37]Lee D H,Jin S G,Cai S,et al.Repair of methylation damage in DNA and RNA by mammalian AlkB homologues.J Biol Chem,2005,280(47):39448-39459
[38]Pastore C,Topalidou I,Forouhar F,et al.Crystal structure and RNA binding properties of the RNA Recognition Motif(RRM)and AlkB domains of human AlkB Homolog 8(ABH8),an enzyme catalyzing tRNA hyper-modification.J Biol Chem,2012,287(3):2130-2143
[39]Zheng G,Dahl J A,Niu Y,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.Mol Cell,2013,49(1):18-29
[40]Jia G,Yang C G,Yang S,et al.Oxidative demethylation of3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO.FEBS Lett,2008,582(23-24):3313-3319
[41]Jia G,Fu Y,Zhao X,et al.N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.Nat Chem Biol,2011,7(12):885-887
[42]Squires J E,Patel H R,Nousch M,et al.Widespread occurrence of5-methylcytosine in human coding and non-coding RNA.Nucleic Acids Res,2012,40(11):5023-5033
[43]Pan T.N6-methyl-adenosine modification in messenger and long non-coding RNA.Trends Biochem Sci,2013,38(4):204-209
[44]Mayer O,Waldsich C,Grossberger R,et al.Folding of the td pre-RNA with the help of the RNA chaperone StpA.Biochem Soc Trans,2002,30(Pt 6):1175-1180
[45]Kim J H,Lee J M,Lee H N,et al.RNA-binding properties and RNA chaperone activity of human peroxiredoxin 1.Biochem Biophys Res Commun,2012,425(4):730-734
[46]Cui D X,Zeng G Y,Wang F,et al.Mechanism of exogenous nucleic acids and their precursers improving the repair of intestinal epithelium after酌-irradiation in mice.World J Gastroentero,2000,6(5):709-717
[47]Gao W,Li L,Xu P,et al.Frequent down-regulation of hABH2 in gastric cancer and its involvement in growth of cancer cells.J Gastroenterol Hepatol,2011,26(3):577-584
[48]Fujii T,Shimada K,Anai S,et al.ALKBH2,a novel AlkB homologue,contributes to human bladder cancer progression by regulating MUC1 expression.Cancer Sci,2013,104(3):321-327
[49]Tasaki M,Shimada K,Kimura H,et al.ALKBH3,a human AlkB homologue,contributes to cell survival in human non-small-cell lung cancer.Br J Cancer,2011,104(4):700-706
[50]Koike K,Ueda Y,Hase H,et al.Anti-tumor effect of AlkB homolog 3 knockdown in hormone-independent prostate cancer cells.Curr Cancer Drug Targets,2012,12(7):847-856
[2]Chan C M,Zhou C,Huang R H.Reconstituting bacterial RNA repair and modification in vitro.Science,2009,326(5950):247
[3]Amitsur M,Levitz R,Kaufman G.Bacteriophage T4 anticodon nuclease,polynucleotide kinase,and RNA ligase reprocess the host lysine tRNA.EMBOJ,1987,6(8):2499-2503
[4]Klaiman D,Kaufmann G.Phage T4-induced dTTP accretion bolsters a tRNase-based host defense.Virology,2011,414(1):97-101
[5]Abelson J,Trotta C R,Li H.tRNA splicing.J Biol Chem,1998,273(21):12685-12688
[6]Sidrauski C,Cox J S,Walter P.tRNA ligase is required for regulated mRNA splicing in the unfolded protein response.Cell,1996,87(3):405-413
[7]Wang L K,Lima C D,Shuman S.Structure and mechanism of T4polynucleotide kinase:an RNA repair enzyme.EMBOJ,2002,21(14):3873-3880
[8]Das U,Shuman S.Mechanism of RNA 2忆,3忆-cyclic phosphate end healing by T4 polynucleotide kinase-phosphatase.Nucleic Acids Res,2013,41(1):355-365
[9]Jayakrishnan N,Beate S,Raffael S,et al.RNA repair:an antidote to cytotoxic eukaryal RNA damage.Mol Cell,2008,31(2):278-286
[10]Cranston J W,Silber R,Malathi V G,et al.Studies on ribonucleic acid ligase:characterization of an adenosine triphosphate-inorganic pyrophosphate exchange reaction and demonstration of an enzyme-adenylate complex with T4 bacteriophage-induced enzyme.J Biol Chem,1974,249(23):7447-7456
[11]Sugino A,Snoper T J,Cozzarelli N R.Bacteriophage T4 RNA ligase.Reaction intermediates and interaction of substrates.J Biol Chem,1977,252(5):1732-1738
[12]Martins A,Shuman S.An end-healing enzyme from Clostridium thermocellum with 5忆kinase,2忆,3忆phosphatese,and adenylyltransferase activities.RNA,2005,11(8):1271-1280
[13]Wang L K,Das U,Smith P,et al.Structure and mechanism of the polynucleotide kinase component of the bacterial Pnkp-Hen1 RNA repair system.RNA,2012,18(12):2277-2286
[14]Paul S,Li Kai W,Pravin A,et al.The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family.Proc Natl Acad Sci USA,2012,109(7):2296-2301
[15]Wang P,Chan C M,Christensen D,et al.Molecular basis of bacterial protein Hen1 activating the ligase activity of bacterial protein Pnkp for RNA repair.Proc Natl Acad Sci USA,2012,109(33):13248-13253
[16]Yu B,Yang Z,Li J,et al.Methylation as a crucial step in plant microRNA biogenesis.Science,2005,307(5711):932-935
[17]Saito K,Sakaguchi Y,Suzuki T,et al.Pimet,the Drosophila homolog of HEN1,mediates 2忆-O-methylation of Piwi-interacting RNAs at their 3忆ends.Genes Dev,2007,21(13):1603-1608
[18]Kamminga L M,Luteijn M J,den Broeder M J,et al.Hen1 is required for oocyte development and piRNA stability in zebrafish.EMBOJ,2010,29(21):3688-3700
[19]Kirino Y,Mourelatos Z.Mouse Piwi-interacting RNAs are 2忆-Omethylated at their 3忆termini.Nat Struct Mol Biol,2007,14(4):347-348
[20]Jain R,Shuman S.Bacterial Hen1 is a 3忆terminal RNA ribose 2忆O-methyltransferase component of a bacterial RNA repair cassette.RNA,2010,16(2):316-323
[21]Jain R,Shuman S.Active site mapping and substrate specificity of bacterial Hen1,a manganese-dependent 3忆-terminal RNA ribose 2忆-O-methyltransferase.RNA,2011,17(3):429-438
[22]Mui Chan C,Zhou C,Brunzelle J S,et al.Structural and biochemical insights into 2忆-O-methylation at the 3忆-terminal nucleotide of RNA by Hen1.Proc Natl Acad Sci USA,2009,106(42):17699-17704
[23]Huang R H.Unique 2忆-O-methylation by Hen1 in eukaryotic RNA interference and bacterial RNA repair.Biochemistry,2012,51(20):4087-4095
[24]Wang L K,Shuman S.Structure-function analysis of yeast tRNA ligase.RNA,2005,11(6):966-975
[25]Sawaya R,Schwer B,Shuman S.Genetic and biochemical analysis of the functional domains of yeast tRNA ligase.J Biol Chem,2003,278(45):43928-43938
[26]Spinelli S L,Consaul S A,Phizicky E M.A conditional lethal yeast phosphotransferase mutant accumulates tRNA with a 2忆-phosphate and an unmodified base at the splice junction.RNA,1997,3(12):1388-1400
[27]Englert M,Beier H.Plant tRNA ligases are multifunctional enzymes that have diverged in sequence and substrate specificity from RNA ligases of other phylogenetic origins.Nucleic Acids Res,2005,33(1):388-399
[28]Wang L K,Schwer B,Englert M,et al.Structure-function analysis of the kinase-CPD domain of yeast tRNA ligase(Trl1)and requirements for complementation of tRNA splicing by a plant Trl1homolog.Nucleic Acids Res,2006,34(2):517-527
[29]Yang C G,Yi C,Duguid E M,et al.Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA.Nature,2008,452(7190):961-966
[30]Aravind L,Koonin E V.The DNA-repair protein AlkB,EGL-9,and leprecan define new families of 2-oxoglu-tarate-and irondependent dioxygenases.Genome Biol,2001,2(3):research0007.1-research0007.8
[31]Falnes P O,Johansen R F,Seeberg E.AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli.Nature,2002,419(6903):178-182
[32]Trewick S C,Henshaw T F,Hausinger R P,et al.Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage.Nature,2002,419(6903):174-178
[33]Ougland R,Zhang C M,Liiv A,et al.AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation.Mol Cell,2004,16(1):107-116
[34]VgbφC B,Svaasand E K,Aas P A,et al.Methylation damage to RNA induced in vivo in Escherichia coli is repaired by endogenous AlkB as part of the adaptive response.DNA Repair(Amst),2013,12(3):188-195
[35]Sundhein O,VgbφC B,Bjφrs M,et al.Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.EMBO J,2006,25(14):3389-3397
[36]Yi C,Yang C G,He C.A non-heme iron-mediated chemical demethylation in DNA and RNA.Acc Chem Res,2009,42(4):519-529
[37]Lee D H,Jin S G,Cai S,et al.Repair of methylation damage in DNA and RNA by mammalian AlkB homologues.J Biol Chem,2005,280(47):39448-39459
[38]Pastore C,Topalidou I,Forouhar F,et al.Crystal structure and RNA binding properties of the RNA Recognition Motif(RRM)and AlkB domains of human AlkB Homolog 8(ABH8),an enzyme catalyzing tRNA hyper-modification.J Biol Chem,2012,287(3):2130-2143
[39]Zheng G,Dahl J A,Niu Y,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.Mol Cell,2013,49(1):18-29
[40]Jia G,Yang C G,Yang S,et al.Oxidative demethylation of3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO.FEBS Lett,2008,582(23-24):3313-3319
[41]Jia G,Fu Y,Zhao X,et al.N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.Nat Chem Biol,2011,7(12):885-887
[42]Squires J E,Patel H R,Nousch M,et al.Widespread occurrence of5-methylcytosine in human coding and non-coding RNA.Nucleic Acids Res,2012,40(11):5023-5033
[43]Pan T.N6-methyl-adenosine modification in messenger and long non-coding RNA.Trends Biochem Sci,2013,38(4):204-209
[44]Mayer O,Waldsich C,Grossberger R,et al.Folding of the td pre-RNA with the help of the RNA chaperone StpA.Biochem Soc Trans,2002,30(Pt 6):1175-1180
[45]Kim J H,Lee J M,Lee H N,et al.RNA-binding properties and RNA chaperone activity of human peroxiredoxin 1.Biochem Biophys Res Commun,2012,425(4):730-734
[46]Cui D X,Zeng G Y,Wang F,et al.Mechanism of exogenous nucleic acids and their precursers improving the repair of intestinal epithelium after酌-irradiation in mice.World J Gastroentero,2000,6(5):709-717
[47]Gao W,Li L,Xu P,et al.Frequent down-regulation of hABH2 in gastric cancer and its involvement in growth of cancer cells.J Gastroenterol Hepatol,2011,26(3):577-584
[48]Fujii T,Shimada K,Anai S,et al.ALKBH2,a novel AlkB homologue,contributes to human bladder cancer progression by regulating MUC1 expression.Cancer Sci,2013,104(3):321-327
[49]Tasaki M,Shimada K,Kimura H,et al.ALKBH3,a human AlkB homologue,contributes to cell survival in human non-small-cell lung cancer.Br J Cancer,2011,104(4):700-706
[50]Koike K,Ueda Y,Hase H,et al.Anti-tumor effect of AlkB homolog 3 knockdown in hormone-independent prostate cancer cells.Curr Cancer Drug Targets,2012,12(7):847-856