反義RNA

反義RNA（Antisense RNA, 常縮寫爲asRNA），是一種與轉錄產物mRNA（信使RNA）互補的單鏈RNA。部分學者亦將這類RNA稱爲「micRNA」（mRNA干擾互補RNA，英語：mRNA-interfering complementary RNA），但此名稱並未得到廣泛使用^[1]。

反義RNA可通過與mRNA結合來抑制轉譯的進行^[2]。可通過化學計量來測定反義RNA的抑制效果。大腸桿菌的R1质粒上的hok/sok系統（英语：hok/sok system）就是反義RNA抑制轉譯的一個實例。反義RNA有很大的作治療疾病的藥物的潛力，惟目前此類藥物只有福米韋生進入市場。一位評論員這樣認爲：「反義RNA牽扯到一大堆技術，看上去『很華麗』，但商業價值卻低得可憐。」^[3]一般來說，目前設計反義RNA（藥物）的效率仍然不高，相關藥物的生物活性也不高。目前也沒有找到高效的給藥途徑^[4]。

反義RNA的起效與RNA干涉（RNAi）有關。只有真核生物具有RNA干涉過程。反義RNA和相應的mRNA形成雙鏈RNA片段爲RNA干涉過程的第一步^[5]。隨後，DICER酶（英语：Dicer）能將上述的雙鏈RNA切成小段。這些小段的反義RNA鏈緊接着會與RNA誘導沉默複合體（RISC）結合，之後，後者便會與小段上的mRNA鏈連接，並將之降解^[6]。一些轉基因植物因能表達反義RNA，RNA干涉途徑處於激活狀態^[7]。因爲反義RNA的表達，RNA干涉會導致不同程度的基因沉默。比較著名的例子有Flavr Savr（英语：Flavr Savr）番茄以及兩種耐環斑（英语：Papaya ringspot virus）的番木瓜^[8]^[9]。

長順式反義RNA的轉錄在哺乳動物中十分常見^[10]。儘管一些上述的反義RNA的功能已被闡明，比如Zeb2/Sipl反義RNA，但目前尚未發現這類RNA的一般功能。Zeb2/Sipl^[11]這一反義RNA在DNA上的對應區域爲與編碼Zeb2 mRNA的區域的5'端非編碼區域的一個內含子上的5'端剪切位點的相對的區域。反義非編碼RNA的表達可以阻止mRNA前體上一個內含子的切除，從而使得相應的mRNA無法與核糖體結合，Zeb2基因因而也就無法表達。長鏈反義非編碼RNA的編碼區域通常與相關蛋白質的編碼區域一致^[12]但更深入的研究表明，mRNA和反義非編碼RNA各自的表達模式相當複雜^[13]^[14]。

參見[编辑]

順式自然反義轉錄（英语：Cis-natural antisense transcript）（Cis-natural antisense transcript）

參考[编辑]

^ 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.
^ 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.
^ 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）.
^ 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
^ 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）.
^ Ross C. Wilson and Jennifer A. Doudna (2013) Molecular Mechanisms of RNA Interference. Annual Review of Biophysics Vol. 42: 217-239 存档副本. [2015-12-16]. （原始内容存档于2021-07-11）.
^ 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）.
^ Sanders RA, Hiatt W. Tomato transgene structure and silencing. Nat Biotechnol. 2005, 23 (3): 287–9. PMID 15765076. doi:10.1038/nbt0305-287b.
^ 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.
^ Katayama S, Tomaru Y, Kasukawa T; et al. Antisense transcription in the mammalian transcriptome. Science. September 2005, 309 (5740): 1564–6. PMID 16141073. doi:10.1126/science.1112009.
^ Beltran M, Puig I, Peña C; et al. 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.
^ Engström PG, Suzuki H, Ninomiya N; et al. Complex Loci in human and mouse genomes. PLoS genetics. April 2006, 2 (4): e47. PMC 1449890 . PMID 16683030. doi:10.1371/journal.pgen.0020047.
^ Dinger ME, Amaral PP, Mercer TR; et al. 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.
^ 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.

[pmid6201848-1] 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.

[DePalma2005-3] 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 存档副本. [2015-12-16]. （原始内容存档于2021-07-11）.

[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）.

[Sanders-8] Sanders RA, Hiatt W. Tomato transgene structure and silencing. Nat Biotechnol. 2005, 23 (3): 287–9. PMID 15765076. doi:10.1038/nbt0305-287b.

[Chiang-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.

[Katayama-10] Katayama S, Tomaru Y, Kasukawa T; et al. Antisense transcription in the mammalian transcriptome. Science. September 2005, 309 (5740): 1564–6. PMID 16141073. doi:10.1126/science.1112009.

[Beltran-11] Beltran M, Puig I, Peña C; et al. 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.

[Engstrom-12] Engström PG, Suzuki H, Ninomiya N; et al. Complex Loci in human and mouse genomes. PLoS genetics. April 2006, 2 (4): e47. PMC 1449890 . PMID 16683030. doi:10.1371/journal.pgen.0020047.

[Dinger-13] Dinger ME, Amaral PP, Mercer TR; et al. 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.

[Mercer-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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