神经系统中LINE-1转座的研究进展
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摘要
长散在核重复序列1(LINE-1)属于逆转录转座子,至今仍在人类基因组中保留自主转座的活性,并在基因组中占有很高的比例,其频繁转座会引起基因组不稳定,导致严重的后果。通常宿主细胞运用多种机制对其转座进行严格控制,所以LINE-1在大多数体细胞中是无活性的,然而近年来有研究证实在神经元细胞中LINE-1可以表达并转座,插入基因组的不同位置,导致每个神经元细胞在基因水平上都是独特的。此外,LINE-1的转座可能在长期记忆等方面具有一定生理学意义,也有可能产生一些病理影响。希望本文能对全面了解LINE-1在神经系统中的情况提供一些线索。
Long interspersed nuclear element 1(LINE-1) belongs to retrotransposon, which is the only currently known active autonomous transposon in human cells. It comprises a large proportion of human genome, and its transposition may induce genetic instability and cause serious consequences. Usually, host cells develope multiple strategies to restrict LINE-1 retrotransposition and LINE-1 is inactive in most somatic cells. However, the nerve cells is an exception:LINE-1 can express and transpose in nerve cells, and each neuron is genetically unique by the fact that LINE-1 can insert into various genomic locations. LINE-1 retrotransposition could contribute to some physiological significance such as long-term memory, on the other hand, the expression of LINE-1 may also have some pathological effects. We hope this paper may shed light on the acknowledgement of function of LINE-1 in the nervous system.
Long interspersed nuclear element 1(LINE-1) belongs to retrotransposon, which is the only currently known active autonomous transposon in human cells. It comprises a large proportion of human genome, and its transposition may induce genetic instability and cause serious consequences. Usually, host cells develope multiple strategies to restrict LINE-1 retrotransposition and LINE-1 is inactive in most somatic cells. However, the nerve cells is an exception:LINE-1 can express and transpose in nerve cells, and each neuron is genetically unique by the fact that LINE-1 can insert into various genomic locations. LINE-1 retrotransposition could contribute to some physiological significance such as long-term memory, on the other hand, the expression of LINE-1 may also have some pathological effects. We hope this paper may shed light on the acknowledgement of function of LINE-1 in the nervous system.
引文
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[2]Goodier JL,Kazazian HH Jr.Retrotransposons revisited:the restraint and rehabilitation of parasites[J].Cell,2008,135(1):23-35.
[3]Richardson SR,Doucet AJ,Kopera HC,et al.The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes[J].Microbiol Spectr,2015,3(2):MDNA3-0061-2014.
[4]刘茜,王瑾晖,李晓宇,等.逆转录转座子LINE-1与肿瘤的发生和发展[J].遗传,2016,38(2):93-102.
[5]Muotri AR,Chu VT,Marchetto MC,et al.Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition[J].Nature,2005,435(7044):903-910.
[6]Upton KR,Gerhardt DJ,Jesuadian JS,et al.Ubiquitous L1mosaicism in hippocampal neurons[J].Cell,2015,161(2):228-239.
[7]Singer T,McConnell MJ,Marchetto MC,et al.LINE-1retrotransposons:mediators of somatic variation in neuronal genomes?[J].Trends Neurosci,2010,33(8):345-354.
[8]Bachiller S,Del-Pozo-Martin Y,Carrion AM.L1 retrotransposition alters the hippocampal genomic landscape enabling memory formation[J].Brain Behav Immun,2017,64:65-70.
[9]Muotri AR,Marchetto MC,Coufal NG,et al.L1 retrotransposition in neurons is modulated by MeCP2[J].Nature,2010,468(7322):443-446.
[10]Bundo M,Toyoshima M,Okada Y,et al.Increased l1retrotransposition in the neuronal genome in schizophrenia[J].Neuron,2014,81(2):306-313.
[11]Doyle GA,Crist RC,Karatas ET,et al.Analysis of LINE-1Elements in DNA from Postmortem Brains of Individuals with Schizophrenia[J].Neuropsychopharmacology,2017,42(13):2602-2611.
[12]Shpyleva S,Melnyk S,Pavliv O,et al.Overexpression of LINE-1 Retrotransposons in Autism Brain[J].Mol Neurobiol,2018,55(2):1740-1749.
[13]Liu S,Du T,Liu Z,et al.Inverse changes in L1 retrotransposons between blood and brain in major depressive disorder[J].Sci Rep,2016,6:37530.
[14]Coufal NG,Garcia-Perez JL,Peng GE,et al.Ataxia telangiectasia mutated(ATM)modulates long interspersed element-1(L1)retrotransposition in human neural stem cells[J].Proc Natl Acad Sci U S A,2011,108(51):20382-20387.
[15]Amir RE,Van den Veyver IB,Wan M,et al.Rett syndrome is caused by mutations in X-linked MECP2,encoding methyl-CpG-binding protein 2[J].Nat Genet,1999,23(2):185-188.
[16]Yu F,Zingler N,Schumann G,et al.Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription[J].Nucleic Acids Res,2001,29(21):4493-4501.
[17]Guffanti G,Gaudi S,Klengel T,et al.LINE1 insertions as a genomic risk factor for schizophrenia:Preliminary evidence from an affected family[J].Am J Med Genet BNeuropsychiatr Genet,2016,171(4):534-545.
[18]Doyle GA,Berrettini WH.Failure to Replicate an Association of a LINE-1 Element in ERI1 Exoribonuclease Family Member 3(ERI3)with Schizophrenia[J].Neuropsychopharmacology,2017,42(13):2471.
[19]Doyle GA,Doucet-O'Hare TT,Hammond MJ,et al.Reading LINEs within the cocaine addicted brain[J].Brain Behav,2017,7(5):e00678.
[20]Coufal NG,Garcia-Perez JL,Peng GE,et al.L1 retrotransposition in human neural progenitor cells[J].Nature,2009,460(7259):1127-1131.
[21]Skene PJ,Illingworth RS,Webb S,et al.Neuronal MeCP2is expressed at near histone-octamer levels and globally alters the chromatin state[J].Mol Cell,2010,37(4):457-468.
[22]Horn AV,Klawitter S,Held U,et al.Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity[J].Nucleic Acids Res,2014,42(1):396-416.
[23]Li X,Zhang J,Jia R,et al.The MOV10 helicase inhibits LINE-1 mobility[J].J Biol Chem,2013,288(29):21148-21160.
[24]Zhao K,Du J,Han X,et al.Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutieres syndrome-related SAMHD1[J].Cell Rep,2013,4(6):1108-1115.
[25]Stetson DB,Ko JS,Heidmann T,et al.Trex1 prevents cell-intrinsic initiation of autoimmunity[J].Cell,2008,134(4):587-598.
[2]Goodier JL,Kazazian HH Jr.Retrotransposons revisited:the restraint and rehabilitation of parasites[J].Cell,2008,135(1):23-35.
[3]Richardson SR,Doucet AJ,Kopera HC,et al.The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes[J].Microbiol Spectr,2015,3(2):MDNA3-0061-2014.
[4]刘茜,王瑾晖,李晓宇,等.逆转录转座子LINE-1与肿瘤的发生和发展[J].遗传,2016,38(2):93-102.
[5]Muotri AR,Chu VT,Marchetto MC,et al.Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition[J].Nature,2005,435(7044):903-910.
[6]Upton KR,Gerhardt DJ,Jesuadian JS,et al.Ubiquitous L1mosaicism in hippocampal neurons[J].Cell,2015,161(2):228-239.
[7]Singer T,McConnell MJ,Marchetto MC,et al.LINE-1retrotransposons:mediators of somatic variation in neuronal genomes?[J].Trends Neurosci,2010,33(8):345-354.
[8]Bachiller S,Del-Pozo-Martin Y,Carrion AM.L1 retrotransposition alters the hippocampal genomic landscape enabling memory formation[J].Brain Behav Immun,2017,64:65-70.
[9]Muotri AR,Marchetto MC,Coufal NG,et al.L1 retrotransposition in neurons is modulated by MeCP2[J].Nature,2010,468(7322):443-446.
[10]Bundo M,Toyoshima M,Okada Y,et al.Increased l1retrotransposition in the neuronal genome in schizophrenia[J].Neuron,2014,81(2):306-313.
[11]Doyle GA,Crist RC,Karatas ET,et al.Analysis of LINE-1Elements in DNA from Postmortem Brains of Individuals with Schizophrenia[J].Neuropsychopharmacology,2017,42(13):2602-2611.
[12]Shpyleva S,Melnyk S,Pavliv O,et al.Overexpression of LINE-1 Retrotransposons in Autism Brain[J].Mol Neurobiol,2018,55(2):1740-1749.
[13]Liu S,Du T,Liu Z,et al.Inverse changes in L1 retrotransposons between blood and brain in major depressive disorder[J].Sci Rep,2016,6:37530.
[14]Coufal NG,Garcia-Perez JL,Peng GE,et al.Ataxia telangiectasia mutated(ATM)modulates long interspersed element-1(L1)retrotransposition in human neural stem cells[J].Proc Natl Acad Sci U S A,2011,108(51):20382-20387.
[15]Amir RE,Van den Veyver IB,Wan M,et al.Rett syndrome is caused by mutations in X-linked MECP2,encoding methyl-CpG-binding protein 2[J].Nat Genet,1999,23(2):185-188.
[16]Yu F,Zingler N,Schumann G,et al.Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription[J].Nucleic Acids Res,2001,29(21):4493-4501.
[17]Guffanti G,Gaudi S,Klengel T,et al.LINE1 insertions as a genomic risk factor for schizophrenia:Preliminary evidence from an affected family[J].Am J Med Genet BNeuropsychiatr Genet,2016,171(4):534-545.
[18]Doyle GA,Berrettini WH.Failure to Replicate an Association of a LINE-1 Element in ERI1 Exoribonuclease Family Member 3(ERI3)with Schizophrenia[J].Neuropsychopharmacology,2017,42(13):2471.
[19]Doyle GA,Doucet-O'Hare TT,Hammond MJ,et al.Reading LINEs within the cocaine addicted brain[J].Brain Behav,2017,7(5):e00678.
[20]Coufal NG,Garcia-Perez JL,Peng GE,et al.L1 retrotransposition in human neural progenitor cells[J].Nature,2009,460(7259):1127-1131.
[21]Skene PJ,Illingworth RS,Webb S,et al.Neuronal MeCP2is expressed at near histone-octamer levels and globally alters the chromatin state[J].Mol Cell,2010,37(4):457-468.
[22]Horn AV,Klawitter S,Held U,et al.Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity[J].Nucleic Acids Res,2014,42(1):396-416.
[23]Li X,Zhang J,Jia R,et al.The MOV10 helicase inhibits LINE-1 mobility[J].J Biol Chem,2013,288(29):21148-21160.
[24]Zhao K,Du J,Han X,et al.Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutieres syndrome-related SAMHD1[J].Cell Rep,2013,4(6):1108-1115.
[25]Stetson DB,Ko JS,Heidmann T,et al.Trex1 prevents cell-intrinsic initiation of autoimmunity[J].Cell,2008,134(4):587-598.