遗传 ›› 2013, Vol. 35 ›› Issue (3): 269-280.doi: 10.3724/SP.J.1005.2013.00269
夏天, 肖丙秀, 郭俊明
收稿日期:
2012-08-08
修回日期:
2012-09-20
出版日期:
2013-03-20
发布日期:
2013-03-25
通讯作者:
郭俊明
E-mail:junmingguo@yahoo.com
基金资助:
国家自然科学基金项目(编号:81171660), 宁波市自然科学基金项目(编号:2012A610207), 宁波市科技创新团队项目(编号:2011B82014), 宁波市重点学科项目(编号:XKL11D2127)和宁波大学优秀学位论文培育基金项目(编号:PY2012004)资助
XIA Tian, XIAO Bing-Xiu, GUO Jun-Ming
Received:
2012-08-08
Revised:
2012-09-20
Online:
2013-03-20
Published:
2013-03-25
摘要: 长链非编码RNA(Long non-coding RNA, lncRNA)通过多种机制发挥其生物学功能, 这些机制包括基因印记、染色质重塑、细胞周期调控、剪接调控、mRNA降解和翻译调控等。lncRNA通过这些作用机制在不同水平进行基因表达调控。在研究lncRNA功能的过程中, 研究方法的建立和应用起着非常重要的作用。目前用于lncRNA研究的主要方法有:微阵列、转录组测序、Northern印迹、实时荧光定量逆转录-聚合酶链反应、荧光原位杂交、RNA干扰和RNA结合蛋白免疫沉淀等。文章着重介绍了3种前沿方法, 即:在线快速预测RNA与蛋白质相互作用的catRAPID、RNA纯化的染色质分离(Chromatin isolation by RNA purification, ChIRP)以及非编码RNA沉默与定位分析技术(Combined knockdown and localization analysis of non-coding RNAs, c-KLAN)。
中图分类号:
夏天,肖丙秀,郭俊明. 长链非编码RNA的作用机制及其研究方法[J]. 遗传, 2013, 35(3): 269-280.
XIA Tian, XIAO Bing-Xiu, GUO Jun-Ming. Acting mechanisms and research methods of long noncoding RNAs[J]. HEREDITAS, 2013, 35(3): 269-280.
[1] Spizzo R, Almeida MI, Colombatti A, Calin GA. Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene, 2012, 31(43): 4577-4587.[2] Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol, 2011, 21(6): 354-361.[3] 于红. 表观遗传学: 生物细胞非编码RNA调控的研究进展. 遗传, 2009, 31(11): 1077-1086.[4] 张绍峰, 李晓荣, 孙传宝, 何玉科. 植物非编码RNA调控春化作用的表观遗传. 遗传, 2012, 34(7): 829-834.[5] 孙强, 黄红艳, 韩骅. ncRNA候选基因spt1的克隆与初步分析. 遗传学报, 2004, 31(5): 485-488.[6] Xiao B, Zhang XJ, Li Y, Tang ZL, Yang SL, Mu YL, Cui WT, Ao H, Li K. Identification, bioinformatic analysis and expression profiling of candidate mRNA-like non-coding RNAs in Sus scrofa. J Genet Genomics, 2009, 36(12): 695-702.[7] Wutz A, Rasmussen TP, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet, 2002, 30(2): 167-174.[8] Gong C, Maquat LE. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements. Nature, 2011, 470(7333): 284-288.[9] Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell, 2009, 33(6): 717-726.[10] Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang YL, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 2010, 464(7291): 1071-1076.[11] Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY. Long noncoding RNA as modular scaffold of histone modification complexes. Science, 2010, 329(5992): 689-693.[12] 宋皓军, 俞秀冲, 夏天, 郭俊明, 肖丙秀. 长链非编码RNA与肿瘤的关系及其临床价值. 中国细胞生物学学报, 2012, 34(7): 704-712.[13] Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet, 2009, 10(3): 155-159.[14] Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell, 2011, 43(6): 904-914.[15] Erdmann VA, Szymanski M, Hochberg A, de Groot N, Barciszewski J. Non-coding, mRNA-like RNAs database Y2K. Nucleic Acids Res, 2000, 28(1): 197-200.[16] Mituyama T, Yamada K, Hattori E, Okida H, Ono Y, Terai G, Yoshizawa A, Komori T, Asai K. The Functional RNA Database 3. 0: databases to support mining and annotation of functional RNAs. Nucleic Acids Res, 2009, 37(Suppl. 1): D89-D92.[17] Dinger ME, Pang KC, Mercer TR, Crowe ML, Grimmond SM, Mattick JS. NRED: a database of long noncoding RNA expression. Nucleic Acids Res, 2009, 37(Suppl. 1): D122-D126.[18] Amaral PP, Clark MB, Gascoigne DK, Dinger ME, Mattick JS. lncRNAdb: a reference database for long noncoding RNAs. Nucleic Acids Res, 2011, 39(Suppl. 1): D146-D151.[19] Liao Q, Xiao H, Bu DC, Xie CY, Miao RY, Luo HT, Zhao GG, Yu KT, Zhao HT, Skogerbø G, Chen RS, Wu ZD, Liu CN, Zhao Y. ncFANs: a web server for functional annotation of long non-coding RNAs. Nucleic Acids Res, 2011, 39(Suppl. 2): W118-W124.[20] Bu DC, Yu KT, Sun SL, Xie CY, Skogerbø G, Miao RY, Xiao H, Liao Q, Luo HT, Zhao GG, Zhao HT, Liu ZY, Liu CN, Chen RS, Zhao Y. NONCODE v3. 0: integrative annotation of long noncoding RNAs. Nucleic Acids Res, 2012, 40(D1): D210-D215.[21] Muers M. RNA: Genome-wide views of long non-coding RNAs. Nat Rev Genet, 2011, 12(11): 742.[22] Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA, 2009, 106(28): 11667-11672.[23] Chu C, Qu K, Zhong FL, Artandi SE, Chang HY. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell, 2011, 44(4): 667-678.[24] Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev, 2011, 25(18): 1915-1927.[25] Arney KL. H19 and Igf2--enhancing the confusion? Trends Genet, 2003, 19(1): 17-23.[26] Lee JT. The X as model for RNA’s niche in epigenomic regulation. Cold Spring Harb Perspect Biol, 2010, 2(9): a003749.[27] Stavropoulos N, Lu N, Lee JT. A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice. Proc Natl Acad Sci USA, 2001, 98(18): 10232-10237.[28] Yap KL, Li SD, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell, 2010, 38(5): 662-674.[29] Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA gas5 is a growth arrest-and starvation- associated repressor of the glucocorticoid receptor. Sci Signal, 2010, 3(107): ra8.[30] Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 2010, 142(3): 409-419.[31] Hung T, Wang YL, Lin MF, Koegel AK, Kotake Y, Grant GD, Horlings HM, Shah N, Umbricht C, Wang P, Kong B, Langerød A, Børresen-Dale AL, Kim SK, van de Vijver M, Sukumar S, Whitfield ML, Kellis M, Xiong Y, Wong DJ, Chang HY. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet, 2011, 43(7): 621-629.[32] Jolly C, Lakhotia SC. Human sat III and Drosophila hsrω transcripts: a common paradigm for regulation of nuclear RNA processing in stressed cells. Nucleic Acids Res, 2006, 34(19): 5508-5514.[33] Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 2010, 39(6): 925-938.[34] Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G III, Kenny PJ, Wahlestedt C. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase. Nat Med, 2008, 14(7): 723-730.[35] 赵丽霞, 赵高平, 周欢敏. 哺乳动物印记域DLK1-DIO3的研究进展. 遗传, 2010, 32(8): 769-778.[36] Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer, 2011, 10: 38.[37] Kelley RL, Kuroda MI. Noncoding RNA genes in dosage compensation and imprinting. Cell, 2000, 103(1): 9-12.[38] Gabory A, Jammes H, Dandolo L. The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays, 2010, 32(6): 473-480.[39] Smits G, Mungall AJ, Griffiths-Jones S, Smith P, Beury D, Matthews L, Rogers J, Pask AJ, Shaw G, Vandeberg JL, Mccarrey JR, Renfree MB, Reik W, Dunham I. Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians. Nat Genet, 2008, 40(8): 971-976.[40] Zhang YH, Tycko B. Monoallelic expression of the human H19 gene. Nat Genet, 1992, 1(1): 40-44.[41] Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature, 2000, 405(6785): 486-489.[42] Schoenherr CJ, Levorse JM, Tilghman SM. CTCF maintains differential methylation at the Igf2/H19 locus. Nat Genet, 2003, 33(1): 66-69.[43] Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science, 2008, 322(5902): 750-756.[44] Lee JT, Davidow LS, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet, 1999, 21(4): 400-404.[45] Faust T, Frankel A, D'orso I. Transcription control by long non-coding RNAs. Transcription, 2012, 3(2): 78-86.[46] Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 2007, 129(7): 1311-1323.[47] Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene. Oncogene, 2011, 30(16): 1956-1962.[48] Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene, 2009, 28(2): 195-208.[49] Wilusz JE, Freier SM, Spector DL. 3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell, 2008, 135(5): 919-932.[50] Bernard D, Prasanth KV, Tripathi V, Colasse S, Nakamura T, Xuan ZY, Zhang MQ, Sedel F, Jourdren L, Coulpier F, Triller A, Spector DL, Bessis A. A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J, 2010, 29(18): 3082-3093.[51] Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, ?upunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J. Characterizing the RNA targets and position- dependent splicing regulation by TDP-43. Nat Neurosci, 2011, 14(4): 452-458.[52] Maquat LE. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol, 2004, 5(2): 89-99.[53] Kim YK, Furic L, Desgroseillers L, Maquat LE. Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay. Cell, 2005, 120(2): 195-208.[54] Kim YK, Furic L, Parisien M, Major F, DesGroseillers L, Maquat LE. Staufen1 regulates diverse classes of mammalian transcripts. EMBO J, 2007, 26(11): 2670-2681.[55] Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 2002, 297(5580): 353-356.[56] Yoon JH, Abdelmohsen K, Srikantan S, Yang XL, Martindale JL, De S, Huarte M, Zhan M, Becker KG, Gorospe M. LincRNA-p21 suppresses target mRNA translation. Mol Cell, 2012, 47(4): 648-655.[57] Yan B, Wang ZH, Guo JT. The research strategies for probing the function of long noncoding RNAs. Genomics, 2012, 99(2): 76-80.[58] Dinger ME, Amaral PP, Mercer TR, Pang KC, Bruce SJ, Gardiner BB, Askarian-Amiri ME, Ru KL, Soldà G, Simons C, Sunkin SM, Crowe ML, Grimmond SM, Perkins AC, Mattick JS. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res, 2008, 18(9): 1433-1445.[59] Mortazavi A, Williams BA, Mccue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods, 2008, 5(7): 621-628.[60] Ørom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang QH, Guigo R, Shiekhattar R. Long noncoding RNAs with enhancer-like function in human cells. Cell, 2010, 143(1): 46-58.[61] Lin MY, Pedrosa E, Shah A, Hrabovsky A, Maqbool S, Zheng DY, Lachman HM. RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS One, 2011, 6(9): e23356.[62] Alwine JC, Kemp DJ, Stark GR. Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. Proc Natl Acad Sci USA, 1977, 74(12): 5350-5354.[63] Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR. Genome Res, 1996, 6(10): 986-994.[64] Furuno M, Pang KC, Ninomiya N, Fukuda S, Frith MC, Bult C, Kai C, Kawai J, Carninci P, Hayashizaki Y, Mattick JS, Suzuki H. Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLoS Genet, 2006, 2(4): e37.[65] Rudkin GT, Stollar BD. High resolution detection of DNA-RNA hybrids in situ by indirect immunofluorescence. Nature, 1977, 265(5593): 472-473.[66] Fire A, Xu SQ, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998, 391(6669): 806-811.[67] Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell, 2008, 32(2): 232-246.[68] Keene JD, Komisarow JM, Friedersdorf MB. RIP-Chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts. Nat Protoc, 2006, 1(1): 302-307.[69] Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT. Genome-wide identification of polycomb-associated RNAs by RIP- seq. Mol Cell, 2010, 40(6): 939-953.[70] Bellucci M, Agostini F, Masin M, Tartaglia GG. Predicting protein associations with long noncoding RNAs. Nat Methods, 2011, 8(6): 444-445.[71] Chakraborty D, Kappei D, Theis M, Nitzsche A, Ding L, Paszkowski-Rogacz M, Surendranath V, Berger N, Schulz H, Saar K, Hubner N, Buchholz F. Combined RNAi and localization for functionally dissecting long noncoding RNAs. Nat Methods, 2012, 9(4): 360-362.[72] Wu T, Wang J, Liu C, Zhang Y, Shi B, Zhu X, Zhang Z, Skogerbo G, Chen L, Lu H, Zhao Y, Chen R. NPInter: the noncoding RNAs and protein related biomacromolecules interaction database. Nucleic Acids Res, 2006, 34(Suppl 1): D150-D152.[73] Maenner S, Blaud M, Fouillen L, Savoye A, Marchand V, Dubois A, Sanglier-Cianferani S, van Dorsselaer A, Clerc P, Avner P, Visvikis A, Branlant C. 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol, 2010, 8(1): e1000276.[74] Chu C, Quinn J, Chang HY. Chromatin isolation by RNA purification (ChIRP). J Vis Exp, 2012, (61): e3912.[75] Franke A, Baker BS. The rox1 and rox2 RNAs are essential components of the compensasome, which mediates dosage compensation in Drosophila. Mol Cell, 1999, 4(1): 117-122.[76] Yang D, Buchholz F, Huang ZD, Goga A, Chen CY, Brodsky FM, Bishop JM. Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells. Proc Natl Acad Sci USA, 2002, 99(15): 9942-9947.[77] Kittler R, Surendranath V, Heninger AK, Slabicki M, Theis M, Putz G, Franke K, Caldarelli A, Grabner H, Kozak K, Wagner J, Rees E, Korn B, Frenzel C, Sachse C, Sonnichsen B, Guo J, Schelter J, Burchard J, Linsley PS, Jackson A L, Habermann B, Buchholz F. Genome-wide resources of endoribonuclease-prepared short interfering RNAs for specific loss-of-function studies. Nat Methods, 2007, 4(4): 337-344.[78] Henschel A, Buchholz F, Habermann B. DEQOR: a web-based tool for the design and quality control of siRNAs. Nucleic Acids Res, 2004, 32(Suppl 2): W113-W120.[79] Itzkovitz S, van Oudenaarden A. Validating transcripts with probes and imaging technology. Nat Methods, 2011, 8(4 Suppl.): S12-S19.[80] Baker M. Long noncoding RNAs: the search for function. Nat Methods, 2011, 8(5): 379-383.[81] Bánfai B, Jia H, Khatun J, Wood E, Risk B, Gundling WE Jr, Kundaje A, Gunawardena HP, Yu YB, Xie L, Krajewski K, Strahl BD, Chen X, Bickel P, Giddings MC, Brown JB, Lipovich L. Long noncoding RNAs are rarely translated in two human cell lines. Genome Res, 2012, 22(9): 1646-1657.[82] Paige JS, Wu KY, Jaffrey SR. RNA mimics of green fluorescent protein. Science, 2011, 333(6042): 642-646.[83] Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol, 2012, 30(1): 99-104. |
[1] | 宁椿游,何梦楠,唐茜子,朱庆,李明洲,李地艳. 基于Hi-C技术哺乳动物三维基因组研究进展[J]. 遗传, 2019, 41(3): 215-233. |
[2] | 张华伟, 孟星宇, 李连峰, 杨玉莹, 仇华吉. 长链非编码RNA——抗病毒天然免疫应答的新兴调控因子[J]. 遗传, 2018, 40(7): 525-533. |
[3] | 周瑞,王以鑫,龙科任,蒋岸岸,金龙. LncRNA调控骨骼肌发育的分子机制及其在家养动物中的研究进展[J]. 遗传, 2018, 40(4): 292-304. |
[4] | 施剑,李艳明,方向东. 长链非编码RNA通过细胞核高级结构调控真核基因表达及其临床意义[J]. 遗传, 2017, 39(3): 189-199. |
[5] | 路畅, 黄银花. 动物长链非编码RNA研究进展[J]. 遗传, 2017, 39(11): 1054-1065. |
[6] | 付洋, 舒在悦, 顾鸣敏. 促通读药物的作用机制与临床应用[J]. 遗传, 2016, 38(7): 623-633. |
[7] | 翟亚男, 许泉, 郭亚, 吴强. 原钙粘蛋白基因簇调控区域中成簇的CTCF结合位点分析[J]. 遗传, 2016, 38(4): 323-336. |
[8] | 李静秋, 杨杰, 周平, 乐燕萍, 龚朝辉. 竞争性内源RNA的生物学功能及其调控[J]. 遗传, 2015, 37(8): 756-764. |
[9] | 黄小庆,李丹丹,吴娟. 植物长链非编码RNA研究进展[J]. 遗传, 2015, 37(4): 344-359. |
[10] | 杨峰, 易凡, 曹慧青, 梁子才, 杜权. 长链非编码RNA研究进展[J]. 遗传, 2014, 36(5): 456-468. |
[11] | 李灵, 宋旭. 长链非编码RNA在生物体中的调控作用[J]. 遗传, 2014, 36(3): 228-236. |
[12] | 施子晗, 李泽琴, 张根发. 植物组蛋白赖氨酸化修饰参与基因表达调控的机理[J]. 遗传, 2014, 36(3): 208-219. |
[13] | 樊春燕, 魏强, 郝志强, 李广林. miRNAs调控lincRNAs的生物信息学预测与功能分析[J]. 遗传, 2014, 36(12): 1226-1234. |
[14] | 杨晓华, 张华峰, 赖江华. 中枢单胺类神经递质在酒精依赖中的分子作用机制[J]. 遗传, 2014, 36(1): 11-20. |
[15] | 张韬 杨足君. 植物基因组DNase I超敏感位点的研究进展[J]. 遗传, 2013, 35(7): 867-874. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||
www.chinagene.cn
备案号:京ICP备09063187号-4
总访问:,今日访问:,当前在线: