流产性转录本及流产性起始的研究现状和进展
|
摘要
流产性转录本(abortive transcript, AT),作为一种特殊的非编码RNA是流产性起始(abortive initiation, AI)的转录产物。流产性起始已被证明是转录起始过程中不可或缺的一步,与RNA聚合酶的结构和RNA转录起始的过程密切相关。流产性起始的意义或者说流产性转录本的作用目前仍然未知,但其发生的高频性及存在的广泛性说明其可能有重要的生物学作用。已有研究表明,4 nt以下的流产性转录本能以引物的形式促进转录,更长的流产性转录本则有转录抑制的作用,还发现一些流产性转录本可能会影响转录终止,但这些研究结果还有待被进一步确认。目前对流产性转录本研究的主要瓶颈是没有方法可以对其进行定性和定量检测。随着检测技术的发展,流产性转录本的生物学功能将被阐释和证明,并有可能成为一种新型生物标志物从而为人类的健康服务。本文就流产性起始和流产性转录本的发现、发生机制、生物学作用以及目前研究中存在的问题等方面进行综述,为进一步了解和研究基因转录调控的分子机制提供依据和参考。
Abortive transcript(AT), as a special type of non-coding RNAs, is a transcriptional product of abortive initiation(AI).Abortive initiation has been shown to be an integral step in the transcription initiation process, and tied to the promoter escape reaction undergone by RNA polymerase at the initiation-elongation transition. Although the significance of transcription initiation and function of abortive transcript is still unknown at present, the generality of their occurrence suggests that they may have an important biological role. Previous studies indicated that the abortive transcripts whose length are less than 4 nt promoted transcription as primers, while the longer ones inhibited transcription. Moreover, some abortive transcripts also affected transcription termination. However, these results need to be further confirmed. At present, the main bottleneck of abortive transcript study is the lack of qualitative and quantitative detection methods. With the development of detection technology, the biological function of abortive transcripts will be revealed and demonstrated, and these short RNAs will become a novel biological marker to serve human health. This article reviewed the discovery,mechanism, biological function and problems in current research on abortive initiation and abortive transcript, which provides a basis and reference for further understanding and research on the mechanism of gene transcriptional regulation.
Abortive transcript(AT), as a special type of non-coding RNAs, is a transcriptional product of abortive initiation(AI).Abortive initiation has been shown to be an integral step in the transcription initiation process, and tied to the promoter escape reaction undergone by RNA polymerase at the initiation-elongation transition. Although the significance of transcription initiation and function of abortive transcript is still unknown at present, the generality of their occurrence suggests that they may have an important biological role. Previous studies indicated that the abortive transcripts whose length are less than 4 nt promoted transcription as primers, while the longer ones inhibited transcription. Moreover, some abortive transcripts also affected transcription termination. However, these results need to be further confirmed. At present, the main bottleneck of abortive transcript study is the lack of qualitative and quantitative detection methods. With the development of detection technology, the biological function of abortive transcripts will be revealed and demonstrated, and these short RNAs will become a novel biological marker to serve human health. This article reviewed the discovery,mechanism, biological function and problems in current research on abortive initiation and abortive transcript, which provides a basis and reference for further understanding and research on the mechanism of gene transcriptional regulation.
引文
[1]沃森J D,贝尔S P,贝克T A,等编著.基因的分子生物学(第七版)[M].杨焕明,夏志,潘庆飞,等译.北京:科学出版社,2009:458-460.
[2]罗伯特·维弗主编.刘进元,李骥,赵广荣等译.分子生物学(第二版)[M].北京:清华大学出版社,2007:122-123.
[3]郑用琏.基础分子生物学(第二版)[M].北京:高等教育出版社,2012:120-152.
[4]Johnston D E,McClure W R.RNA Polymerase[M].New York:Cold Spring Harbor Laboratory,1976:413-428.
[5]Carpousis A J and Gralla J D.Cycling of ribonucleic acid polymerase to produce oligonucleotides during initiation in vitro at the lac UV5 promoter[J].Biochemistry,1980,19(14):3245-3253.
[6]Hsu L M.Monitoring abortive initiation[J].Methods,2009.47(1):25-36.
[7]Goldman S R,Ebright R H,Nickels B E.Direct detection of abortive RNA transcripts in vivo[J].Science,2009,324(5929):927-928.
[8]Murakami K S,Masuda S,Darst S A.Structural basis of transcription initiation:RNA polymerase holoenzyme at 4A resolution[J].Science,2002,296(5571):1280-1284.
[9]Bochkareva A,Zenkin N.The sigma70 region 1.2 regulates promoter escape by unwinding DNA downstream of the transcription start site[J].Nucleic Acids Res.,2013,41(8):4565-4572.
[10]Bae B,Feklistov A,Lass-Napiorkowska A,et al.Structure of a bacterial RNA polymerase holoenzyme open promoter complex[J].Elife,2015,4.
[11]Basu R S,Warner B A,Molodtsov V,et al.Structural basis of transcription initiation by bacterial RNA polymerase holoenzyme[J].J Biol Chem.,2014,289(35):24549-24559.
[12]Pupov D,Kuzin I,Bass I,et al.Distinct functions of the RNA polymerase sigma subunit region 3.2 in RNA priming and promoter escape[J].Nucleic Acids Res.,2014,42(7):4494-4504.
[13]Yurieva O,Nikiforov V Jr,Nikiforov V,et al.Insights into RNA polymerase catalysis and adaptive evolution gained from mutational analysis of a locus conferring rifampicin resistance[J].Nucleic Acids Res.,2017,45(19):11327-11340.
[14]Kapanidis A N,Margeat E,Ho S O,et al.Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism[J].Science,2006,314(5802):1144-1147.
[15]Lerner E,Ingargiola A,Lee J J,et al.Different types of pausing modes during transcription initiation[J].Transcription,2017,8(4):242-253.
[16]Leibfried M L,Bavister B D.Effects of epinephrine and hypotaurine on in vitro fertilization in the golden hamster[J].J Reprod Fertil.,1982,66(1):87-93.
[17]Brunner M,Bujard H.Promoter recognition and promoter strength in the Escherichia coli system[J].Embo j.,1987,6(10):3139-3144.
[18]Hsu L M,Cobb I M,Ozmore J R,et al.Initial transcribed sequence mutations specifically affect promoter escape properties[J].Biochemistry,2006,45(29):8841-8854.
[19]Hsu L M,Vo N V,Chamberlin M J.Escherichia coli transcript cleavage factors GreA and GreB stimulate promoter escape and gene expression in vivo and in vitro[J].Proc Natl Acad Sci U S A.,1995,92(25):11588-11592.
[20]Sen R,Nagai H,Shimamoto N.Conformational switching of Escherichia coli RNA polymerase-promoter binary complex is facilitated by elongation factor GreA and GreB[J].Genes Cells,2001,6(5):389-401.
[21]Wiesler S C,Werner F,Weinzierl R O.Promoter independent abortive transcription assays unravel functional interactions between TFIIB and RNA polymerase[J].Methods Mol Biol.,2013,977:217-227.
[22]Di Nocera P P,Avitabile A,Blasi F.In vitro transcription of the Escherichia coli histidine operon primed by dinucleotides.Effect of the first histidine biosynthetic enzyme[J].JBiol Chem.,1975,250(21):8376-8381.
[23]Grachev M A,Zaychikov E F,Ivanova E M,et al.Oligonucleotides complementary to a promoter over the region-8...+2 as transcription primers for E.coli RNA polymerase[J].Nucleic Acids Res.,1984,12(22):8509-8524.
[24]Hoffman D J,Niyogi S K.RNA initiation with dinucleoside monophosphates during transcription of bacteriophage T4DNA with RNA polymerase of Escherichia coli[J].Proc Natl Acad Sci U S A.,1973,70(2):574-578.
[25]Learned R M,Tjian R.In vitro transcription of human ribosomal RNA genes by RNA polymerase I[J].J Mol Appl Genet.,1982,1(6):575-584.
[26]Minkley E G,Pribnow D.Transcription of the early region of bacteriophage T7:selective initiation with dinucleotides[J].J Mol Biol.,1973,77(2):255-277.
[27]Niyogi S K,Stevens A.Studies of the ribonucleic acid polymerase from escherichia coli.iv.effect of oligonucleotides on the ribonucleic acid polymerase reaction with synthetic polyribonucleotides as templates[J].J Biol Chem.,1965,240:2593-2598.
[28]Ruetsch N,Dennis D.RNA polymerase.Limit cognate primer for initiation and stable ternary complex formation[J].J Biol Chem.,1987,262(4):1674-1679.
[29]Samuels M,Fire A,Sharp P A.Dinucleotide priming of transcription mediated by RNA polymerase II[J].J Biol Chem.,1984,259(4):2517-2525.
[30]Smagowicz W,Scheit K H.A minimal mechanism for abortive initiation of transcription of T7 DNA[J].Nucleic Acids Res.,1981,9(21):5845-5854.
[31]Goldman S R,Sharp J S,Vvedenskaya I O,et al.NanoR-NAs prime transcription initiation in vivo[J].Mol Cell.,2011,42(6):817-825.
[32]Druzhinin S Y,Tran N T,Skalenko K S,et al.A Conserved Pattern of Primer-Dependent Transcription Initiation in Escherichia coli and Vibrio cholerae Revealed by 5'RNA-seq[J].PLoS Genet.,2015,11(7):e1005348.
[33]Matsumoto J.Evolutionary role of abortive transcript as a primer for DNA replication[J].J Mol Evol.,1994,39(6):620-624.
[34]Qin S W,Zhao LF.Four-nucleotide and six-nucleotide abortive transcripts can inhibit transcription[J].8th International Conference on Information Technology in Medicine and Education,2016,176-181.
[35]Lee S,Nguyen H M,Kang C.Tiny abortive initiation transcripts exert antitermination activity on an RNA hairpindependent intrinsic terminator[J].Nucleic Acids Res.,2010,38(18):6045-6053.
[36]Liu X,Bushnell D A,Silva D A,et al.Initiation complex structure and promoter proofreading[J].Science,2011,333(6042):633-637.
[37]Kaur H,Arora A,Wengel J,et al.Thermodynamic,counterion,and hydration effects for the incorporation of locked nucleic acid nucleotides into DNA duplexes[J].Nucleic Acids Symp Ser(Oxf).,2008,45(23):7347-7355.29
[2]罗伯特·维弗主编.刘进元,李骥,赵广荣等译.分子生物学(第二版)[M].北京:清华大学出版社,2007:122-123.
[3]郑用琏.基础分子生物学(第二版)[M].北京:高等教育出版社,2012:120-152.
[4]Johnston D E,McClure W R.RNA Polymerase[M].New York:Cold Spring Harbor Laboratory,1976:413-428.
[5]Carpousis A J and Gralla J D.Cycling of ribonucleic acid polymerase to produce oligonucleotides during initiation in vitro at the lac UV5 promoter[J].Biochemistry,1980,19(14):3245-3253.
[6]Hsu L M.Monitoring abortive initiation[J].Methods,2009.47(1):25-36.
[7]Goldman S R,Ebright R H,Nickels B E.Direct detection of abortive RNA transcripts in vivo[J].Science,2009,324(5929):927-928.
[8]Murakami K S,Masuda S,Darst S A.Structural basis of transcription initiation:RNA polymerase holoenzyme at 4A resolution[J].Science,2002,296(5571):1280-1284.
[9]Bochkareva A,Zenkin N.The sigma70 region 1.2 regulates promoter escape by unwinding DNA downstream of the transcription start site[J].Nucleic Acids Res.,2013,41(8):4565-4572.
[10]Bae B,Feklistov A,Lass-Napiorkowska A,et al.Structure of a bacterial RNA polymerase holoenzyme open promoter complex[J].Elife,2015,4.
[11]Basu R S,Warner B A,Molodtsov V,et al.Structural basis of transcription initiation by bacterial RNA polymerase holoenzyme[J].J Biol Chem.,2014,289(35):24549-24559.
[12]Pupov D,Kuzin I,Bass I,et al.Distinct functions of the RNA polymerase sigma subunit region 3.2 in RNA priming and promoter escape[J].Nucleic Acids Res.,2014,42(7):4494-4504.
[13]Yurieva O,Nikiforov V Jr,Nikiforov V,et al.Insights into RNA polymerase catalysis and adaptive evolution gained from mutational analysis of a locus conferring rifampicin resistance[J].Nucleic Acids Res.,2017,45(19):11327-11340.
[14]Kapanidis A N,Margeat E,Ho S O,et al.Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism[J].Science,2006,314(5802):1144-1147.
[15]Lerner E,Ingargiola A,Lee J J,et al.Different types of pausing modes during transcription initiation[J].Transcription,2017,8(4):242-253.
[16]Leibfried M L,Bavister B D.Effects of epinephrine and hypotaurine on in vitro fertilization in the golden hamster[J].J Reprod Fertil.,1982,66(1):87-93.
[17]Brunner M,Bujard H.Promoter recognition and promoter strength in the Escherichia coli system[J].Embo j.,1987,6(10):3139-3144.
[18]Hsu L M,Cobb I M,Ozmore J R,et al.Initial transcribed sequence mutations specifically affect promoter escape properties[J].Biochemistry,2006,45(29):8841-8854.
[19]Hsu L M,Vo N V,Chamberlin M J.Escherichia coli transcript cleavage factors GreA and GreB stimulate promoter escape and gene expression in vivo and in vitro[J].Proc Natl Acad Sci U S A.,1995,92(25):11588-11592.
[20]Sen R,Nagai H,Shimamoto N.Conformational switching of Escherichia coli RNA polymerase-promoter binary complex is facilitated by elongation factor GreA and GreB[J].Genes Cells,2001,6(5):389-401.
[21]Wiesler S C,Werner F,Weinzierl R O.Promoter independent abortive transcription assays unravel functional interactions between TFIIB and RNA polymerase[J].Methods Mol Biol.,2013,977:217-227.
[22]Di Nocera P P,Avitabile A,Blasi F.In vitro transcription of the Escherichia coli histidine operon primed by dinucleotides.Effect of the first histidine biosynthetic enzyme[J].JBiol Chem.,1975,250(21):8376-8381.
[23]Grachev M A,Zaychikov E F,Ivanova E M,et al.Oligonucleotides complementary to a promoter over the region-8...+2 as transcription primers for E.coli RNA polymerase[J].Nucleic Acids Res.,1984,12(22):8509-8524.
[24]Hoffman D J,Niyogi S K.RNA initiation with dinucleoside monophosphates during transcription of bacteriophage T4DNA with RNA polymerase of Escherichia coli[J].Proc Natl Acad Sci U S A.,1973,70(2):574-578.
[25]Learned R M,Tjian R.In vitro transcription of human ribosomal RNA genes by RNA polymerase I[J].J Mol Appl Genet.,1982,1(6):575-584.
[26]Minkley E G,Pribnow D.Transcription of the early region of bacteriophage T7:selective initiation with dinucleotides[J].J Mol Biol.,1973,77(2):255-277.
[27]Niyogi S K,Stevens A.Studies of the ribonucleic acid polymerase from escherichia coli.iv.effect of oligonucleotides on the ribonucleic acid polymerase reaction with synthetic polyribonucleotides as templates[J].J Biol Chem.,1965,240:2593-2598.
[28]Ruetsch N,Dennis D.RNA polymerase.Limit cognate primer for initiation and stable ternary complex formation[J].J Biol Chem.,1987,262(4):1674-1679.
[29]Samuels M,Fire A,Sharp P A.Dinucleotide priming of transcription mediated by RNA polymerase II[J].J Biol Chem.,1984,259(4):2517-2525.
[30]Smagowicz W,Scheit K H.A minimal mechanism for abortive initiation of transcription of T7 DNA[J].Nucleic Acids Res.,1981,9(21):5845-5854.
[31]Goldman S R,Sharp J S,Vvedenskaya I O,et al.NanoR-NAs prime transcription initiation in vivo[J].Mol Cell.,2011,42(6):817-825.
[32]Druzhinin S Y,Tran N T,Skalenko K S,et al.A Conserved Pattern of Primer-Dependent Transcription Initiation in Escherichia coli and Vibrio cholerae Revealed by 5'RNA-seq[J].PLoS Genet.,2015,11(7):e1005348.
[33]Matsumoto J.Evolutionary role of abortive transcript as a primer for DNA replication[J].J Mol Evol.,1994,39(6):620-624.
[34]Qin S W,Zhao LF.Four-nucleotide and six-nucleotide abortive transcripts can inhibit transcription[J].8th International Conference on Information Technology in Medicine and Education,2016,176-181.
[35]Lee S,Nguyen H M,Kang C.Tiny abortive initiation transcripts exert antitermination activity on an RNA hairpindependent intrinsic terminator[J].Nucleic Acids Res.,2010,38(18):6045-6053.
[36]Liu X,Bushnell D A,Silva D A,et al.Initiation complex structure and promoter proofreading[J].Science,2011,333(6042):633-637.
[37]Kaur H,Arora A,Wengel J,et al.Thermodynamic,counterion,and hydration effects for the incorporation of locked nucleic acid nucleotides into DNA duplexes[J].Nucleic Acids Symp Ser(Oxf).,2008,45(23):7347-7355.29
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |