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反义RNA

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反义RNA(Antisense RNA, 常缩写为asRNA),是一种与转录产物mRNA(信使RNA)互补的单链RNA。部分学者亦将这类RNA称为“micRNA”(mRNA干扰互补RNA,英语:mRNA-interfering complementary RNA),但此名称并未得到广泛使用[1]

反义RNA可通过与mRNA结合来抑制转译的进行[2]。可通过化学计量来测定反义RNA的抑制效果。大肠杆菌的R1质粒上的hok/sok 系统英语hok/sok system就是反义RNA抑制转译的一个实例。反义RNA有很大的作治疗疾病的药物的潜力,惟目前此类药物只有福米韦生进入市场。一位评论员这样认为:“反义RNA牵扯到一大堆技术,看上去‘很华丽’,但商業價值却低得可怜。”[3]一般来说,目前设计反义RNA(药物)的效率仍然不高,相关药物的生物活性也不高。目前也没有找到高效的给药途径[4]

反义RNA的起效与RNA干涉(RNAi)有关。只有真核生物具有RNA干涉过程。反义RNA和相应的mRNA形成双链RNA片段为RNA干涉过程的第一步[5]。随后,DICER酶英语Dicer能将上述的双链RNA切成小段。这些小段的反义RNA链紧接着会与RNA诱导沉默复合体(RISC)结合,之后,后者便会与小段上的mRNA链连接,并将之降解[6]。一些转基因植物因能表达反义RNA,RNA干涉途径处于激活状态[7]。因为反义RNA的表达,RNA干涉会导致不同程度的基因沉默。比较著名的例子有Flavr Savr英语Flavr Savr番茄以及两种耐环斑英语Papaya ringspot virus的番木瓜[8][9]

长顺式反义RNA的转录在哺乳动物中十分常见[10]。尽管一些上述的反义RNA的功能已被阐明,比如Zeb2/Sipl反义RNA,但目前尚未发现这类RNA的一般功能。Zeb2/Sipl[11]这一反义RNA在DNA上的对应区域为与编码Zeb2 mRNA的区域的5'端非编码区域的一个内含子上的5'端剪切位点的相对的区域。反义非编码RNA的表达可以阻止mRNA前体上一个内含子的切除,从而使得相应的mRNA无法与核糖体结合,Zeb2基因因而也就无法表达。长链反义非编码RNA的编码区域通常与相关蛋白质的编码区域一致[12]但更深入的研究表明,mRNA和反义非编码RNA各自的表达模式相当复杂[13][14]

参见

参考

  1. ^ Mizuno, T.; Chou, M. Y.; Inouye, M. A unique mechanism regulating gene expression: Translational inhibition by a complementary RNA transcript (micRNA). Proceedings of the National Academy of Sciences of the United States of America. 1984, 81 (7): 1966–1970. PMC 345417. PMID 6201848. doi:10.1073/pnas.81.7.1966. 
  2. ^ Weiss, B; Davidkova, G; Zhou, LW. Antisense RNA gene therapy for studying and modulating biological processes.. Cellular and molecular life sciences : CMLS. March 1999, 55 (3): 334–58. PMID 10228554. doi:10.1007/s000180050296. 
  3. ^ DePalma, Angelo. Twenty-Five Years of Biotech Trends. Genetic Engineering News 25 (14) (Mary Ann Liebert). August 2005: 1, 14–23 [2008-08-17]. ISSN 1935-472X. (原始内容存档于2009-08-17). 
  4. ^ Antisense Oligonucleotides: Basic Concepts and Mechanisms 页面存档备份,存于互联网档案馆 Nathalie Dias and C. A. Stein. Columbia University, New York, New York 10032
  5. ^ Ennio Giordano1, Rosaria Rendina, Ivana Peluso and Maria Furia. RNAi Triggered by Symmetrically Transcribed Transgenes in Drosophila melanogaster. Genetics February 1, 2002 vol. 160 no. 2 637-648 存档副本. [2015-12-16]. (原始内容存档于2016-03-04). 
  6. ^ Ross C. Wilson and Jennifer A. Doudna (2013) Molecular Mechanisms of RNA Interference. Annual Review of Biophysics Vol. 42: 217-239 http://www.annualreviews.org/doi/full/10.1146/annurev-biophys-083012-130404.  缺少或|title=为空 (帮助)
  7. ^ The Flavr Savr Tomato, an Early Example of RNAi Technology Elysia K. Krieger, Edwards Allen, Larry A. Gilbertson, James K. Roberts, William Hiatt, and Rick A. Sanders HortScience June 2008 43:962-964 存档副本. [2015-12-16]. (原始内容存档于2016-03-20). 
  8. ^ Sanders RA, Hiatt W. Tomato transgene structure and silencing. Nat Biotechnol. 2005, 23 (3): 287–9. PMID 15765076. doi:10.1038/nbt0305-287b. 
  9. ^ Chiang CH, Wang JJ, Jan FJ, Yeh SD, Gonsalves D. Comparative reactions of recombinant papaya ringspot viruses with chimeric coat protein (CP) genes and wild-type viruses on CP-transgenic papaya. J. Gen. Virol. November 2001, 82 (Pt 11): 2827–36. PMID 11602796. 
  10. ^ Katayama S, Tomaru Y, Kasukawa T; 等. Antisense transcription in the mammalian transcriptome. Science. September 2005, 309 (5740): 1564–6. PMID 16141073. doi:10.1126/science.1112009. 
  11. ^ Beltran M, Puig I, Peña C; 等. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes & Development. March 2008, 22 (6): 756–69. PMC 2275429. PMID 18347095. doi:10.1101/gad.455708. 
  12. ^ Engström PG, Suzuki H, Ninomiya N; 等. Complex Loci in human and mouse genomes. PLoS genetics. April 2006, 2 (4): e47. PMC 1449890. PMID 16683030. doi:10.1371/journal.pgen.0020047. 
  13. ^ Dinger ME, Amaral PP, Mercer TR; 等. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Research. September 2008, 18 (9): 1433–45. PMC 2527704. PMID 18562676. doi:10.1101/gr.078378.108. 
  14. ^ Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS. Specific expression of long noncoding RNAs in the mouse brain. Proceedings of the National Academy of Sciences of the United States of America. January 2008, 105 (2): 716–21. PMC 2206602. PMID 18184812. doi:10.1073/pnas.0706729105. 
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反义RNA
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