R环的形成及对基因组稳定性的影响

doi:10.3724/SP.J.1005.2014.1185

遗传 ›› 2014, Vol. 36 ›› Issue (12): 1185-1194.doi: 10.3724/SP.J.1005.2014.1185

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R环的形成及对基因组稳定性的影响

潘学峰^{1, 2}, 姜楠¹, 陈细芳¹, 周晓宏¹, 丁良², 段斐²

1. 北京理工大学生命学院, 北京 100081;
2. 河北大学基础医学院, 保定 071002

收稿日期:2014-04-01 出版日期:2014-12-20 发布日期:2014-12-20
作者简介:潘学峰, 博士, 教授, 研究方向：分子遗传学。
基金资助:
徐进, 副教授, 硕士生导师, 研究方向：分子进化与疾病遗传学。E-mail: xujin1@nbu.edu.cn

R-loop structure: the formation and the effects on genomic stability

Xuefeng Pan^{1, 2}, Nan Jiang¹, Xifang Chen¹, Xiaohong Zhou¹, Liang Ding², Fei Duan²

1. School of Life Science, Beijing Institute of Technology, Beijing 100081, China;
2. School of Basic Medicine, Hebei University, Baoding 071002, China

Received:2014-04-01 Online:2014-12-20 Published:2014-12-20

摘要/Abstract

摘要： R-环是由一个RNA:DNA杂交体和一条单链状态的DNA分子共同组成的三链核酸结构。其中, RNA:DNA杂交体的形成起因于基因转录所合成的RNA分子不能与模板分开, 或RNA分子重新与一段双链DNA分子中的一条链杂交。在基因转录过程中, 当转录泡遇到富含G碱基的非模板链区或位于某些与人类疾病有关的三核苷酸卫星DNA时, 转录泡后方累积的负超螺旋可促进R环形成。同时, 新生RNA分子未被及时加工、成熟或未被快速转运到细胞质等因素也会催生R环。研究表明, 细胞拥有多种管理R环的方法, 可以有效地管理R环的形成和处理已经形成的R环, 以尽量避免R环对DNA复制、基因突变和同源重组产生不利影响。文章重点分析了R-环的形成机制及R环对DNA复制、基因突变和同源重组的影响, 并针对R-环诱导的DNA复制在某些三核苷酸重复扩增有关的神经肌肉退行性疾病发生过程中的作用进行了分析和讨论。

关键词: RNA:DNA杂交体, R-环, 基因转录, DNA复制, 基因组稳定性

Abstract: R-loop is a type of three-stranded nucleic acid structure that is made up of an RNA:DNA hybrid, formed due to failing separation of a nascent RNA molecule with transcripting template in transcription or by the re-annealing of RNA molecule with one of the two strands in a double stranded DNA molecule, along with the single stranded DNA, which is either the non-template strand in the transcription bubble or the RNA substituted DNA strand. Formation of R-loops can occur when transcription goes through a genomic DNA region having a tract of G bases in the non-template strand in the transcription bubble or through a type of triplet microsatellite DNA sequences that are known to be associated with certain human diseases. The negative supercoiling forces accumulated in the transcription bubble, and the misprocessing of RNA precursors, as well as the delayed utilizations and transportations of RNA molecules to cytoplasm promote R loop formation. Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated. In this review, we summarize the formation and the impacts of R-loops on DNA replication, mutation rates and the frequencies of homologous recombination, and also discusse the possible role of the R-loop induced DNA replication in mediating trinucleotide repeat expansions as seen with those frequently associated with human neuromuscular degenerative diseases.

Key words: RNA:DNA hybrid, R-loop, gene transcription, DNA replication, genome stability

潘学峰, 姜楠, 陈细芳, 周晓宏, 丁良, 段斐. R环的形成及对基因组稳定性的影响[J]. 遗传, 2014, 36(12): 1185-1194.

Xuefeng Pan, Nan Jiang, Xifang Chen, Xiaohong Zhou, Liang Ding, Fei Duan. R-loop structure: the formation and the effects on genomic stability[J]. HEREDITAS(Beijing), 2014, 36(12): 1185-1194.

参考文献

[1] Helmrich A, Ballarino M, Nudler E, Tora L. Transcription-replication encounters, consequences and genomic instability. Nat Struct Mol Biol, 2013, 20(4): 412–418.
[2] Aguilera A, García-Muse T. R Loops: From transcription byproducts to threats to genome stability. Mol Cell, 2012, 46(2): 115–124.
[3] Lin YL, Pasero P. Interference between DNA replication and transcription as a cause of genomic instability. Curr Genomics, 2012, 13(1): 65–73.
[4] Cook PR. The organization of replication and transcription. Science, 1999, 284(5421): 1790–1795.
[5] Kogoma T. Stable DNA Replication: Interplay between DNA replication, homologous recombination, and transcription. Microbiol Mol Biol Rev, 1997, 61(2): 212–238.
[6] Masai H, Arai K. Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in Escherichia coli. Biochimie, 1996, 78(11–12): 1109–1117.
[7] Roy D, Lieber MR. G clustering is important for the initiation of transcription-induced R-loops in vitro, whereas high G density without clustering is sufficient thereafter. Mol Cell Biol, 2009, 29(11): 3124–3133.
[8] Kim N, Jinks-Robertson S. Guanine repeat-containing sequences confer transcription-dependent instability in an orientation-specific manner in yeast. DNA Repair (Amst), 2011, 10(9): 953–960.
[9] Duquette ML, Handa P, Vincent JA, Taylor AF, Maizels N. Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev, 2004, 18(13): 1618–1629.
[10] Krasilnikova MM, Samadashwily GM, Krasilnikov AS, Mirkin SM. Transcription through a simple DNA repeat blocks replication elongation. EMBO J, 1998, 17(17): 5095–5102.
[11] Belotserkovskii BP, Neil AJ, Saleh SS, Shin JHS, Mirkin SM, Hanawalt PC. Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks. Nucleic Acids Res, 2013, 41(3): 1817–1828.
[12] Roy D, Zhang Z, Lu ZF, Hsieh CL, Lieber MR. Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site. Mol Cell Biol, 2010, 30(1): 146–159.
[13] Wongsurawat T, Jenjaroenpun P, Kwoh CK, Kuznetsov V. Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity. Nucleic Acids Res, 2012, 40( 2): e16.
[14] Shaw NN, Arya DP. Recognition of the unique structure of DNA: RNA hybrids. Biochimie, 2008, 90(7): 1026–1039.
[15] Roberts RW, Crothers DM. Stability and properties of double and triple helices: dramatic effects of RNA or DNA backbone composition. Science, 1992, 258(5087): 1463–1466.
[16] Molina-Navarro MM, Martinez-Jimenez CP, Rodriguez- Navarro S. Transcriptional elongation and mRNA export are coregulated processes. Genet Res Int, 2011: 652461.
[17] Borukhov S, Lee J, Laptenko O. Bacterial transcription elongation factors: new insights into molecular mechanism of action. Mol Microbiol, 2005, 55(5): 1315–1324.
[18] Washburna RS, Gottesman ME. Transcription termination maintains chromosome integrity. Proc Natl Acad Sci USA, 2011, 108(2): 792–797.
[19] Jimeno S, Rondón AG, Luna R, Aguilera A. The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability. EMBO J, 2002, 21(13): 3526–3535.
[20] Li XL, Manley JL. Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell, 2005, 122: 365–378.
[21] Skourti-Stathaki K, Proudfoot NJ, Gromak N. Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol Cell, 2011, 42(6): 794–805.
[22] Gómez-González B, García-Rubio M, Bermejo R, Gaillard H, Shirahige K, Marín A, Foiani M, Aguilera A. Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles. EMBO J, 2011, 30(15): 3106–3119.
[23] Stitt BL.

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R环的形成及对基因组稳定性的影响

R-loop structure: the formation and the effects on genomic stability

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