小分子干扰核糖核酸
小分子干扰核糖核酸(英語:small interfering RNA,缩写为siRNA),又译为小干擾核糖核酸,又称短干擾核糖核酸(short interfering RNA)或沉默核糖核酸(silencing RNA),是長度20到25個核苷酸的雙股RNA,在生物學上有許多不同的用途。目前已知siRNA主要參與RNA干擾(RNAi)現象,以帶有專一性的方式調節基因的表達。此外,也參與一些與RNAi相關的反應途徑,例如抗病毒機制或是染色質結構的改變。不過這些複雜機制的反應途徑目前尚未明瞭。 siRNA最早是由英國的戴维·鲍尔库姆(David Baulcombe)團隊發現,是植物中的後轉錄基因沉默(post-transcriptional gene silencing;PTGS)現象的一部分[1],其研究結果發表於《科學》[2]。2001年,湯瑪士·涂許爾(Thomas Tuschl)團隊發現合成的siRNA,可誘導哺乳動物體內的RNAi作用[3],結果發表於《自然》[4]。這項發現引發了利用可控制的RNAi,來進行生物醫學研究與藥物開發的方法。
![](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/a/a9/SiRNAvitro.gif/300px-SiRNAvitro.gif)
結構
siRNA通常是一段長21個核苷酸的雙股RNA(dsRNA),其兩股分別在RNA的兩端超出另一端2個核苷酸,圖示如下:
每一股各有一個5'磷酸基末端與一個3'羥基末端。此結構經dicer作用而得,dicer這種酶將較長的雙股RNA或小髮夾RNA(small hairpin RNA)切成siRNA[5]。此外,siRNA也可經由多種不同轉染(transfection)技術導入細胞內,並對特定基因產生具專一性的基因敲落(knockdown)效果。本質上,任何已知序列的基因都可以、也因此是經過適當剪裁而具有序列互補性的siRNA的作用對象。這使siRNA成為研究基因功能與藥物目標的一項重要工具。
參考文獻
引用
- ^ Hamilton A,; Baulcombe D. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science. 1999, 286 (5441): 950–2. PMID 10542148.
- ^ Hamilton A, Baulcombe D. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science. 1999, 286 (5441): 950–2. PMID 10542148.
- ^ Elbashir S, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001, 411 (6836): 494–8. PMID 11373684.
- ^ Elbashir S, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001, 411 (6836): 494–8. PMID 11373684.
- ^ Bernstein E, Caudy A, Hammond S, Hannon G. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001, 409 (6818): 363–6. PMID 11201747.
来源
- 概觀
- Hannon G, Rossi J. Unlocking the potential of the human genome with RNA interference. Nature. 2004, 431 (7006): 371–8 [2007-11-24]. PMID 15372045. (原始内容存档于2017-05-06).
- Fire A, Xu S, Montgomery M, Kostas S, Driver S, Mello C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998, 391 (6669): 806–11. PMID 9486653. The original paper by Fire et al. describing RNAi
- Elbashir S, Lendeckel W, Tuschl T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 2001, 15 (2): 188–200 [2007-11-24]. PMID 11157775. (原始内容存档于2008-05-16).
- Zamore P, Tuschl T, Sharp P, Bartel D. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000, 101 (1): 25–33. PMID 10778853.[永久失效連結]
- Hamilton A, Baulcombe D. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science. 1999, 286 (5441): 950–2. PMID 10542148. First description of siRNAs.
- 非專一性效用
- Zhang Z, Weinschenk T, Guo K, Schluesener H. siRNA binding proteins of microglial cells: PKR is an unanticipated ligand. J Cell Biochem. 2006, 97 (6): 1217–29. PMID 16315288.[永久失效連結]
- Kim D, Behlke M, Rose S, Chang M, Choi S, Rossi J. Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol. 2005, 23 (2): 222–6 [2007-11-24]. PMID 15619617. (原始内容存档于2017-03-22).
- Sledz C, Williams B. RNA interference and double-stranded-RNA-activated pathways. Biochem Soc Trans. 2004, 32 (Pt 6): 952–6. PMID 15506933.
- Pebernard, Stephanie; Iggo, Richard D. Determinants of interferon-stimulated gene induction by RNAi vectors. Differentiation; research in biological diversity (Elsevier BV). 2004, 72 (2-3): 103–111. ISSN 0301-4681. PMID 15066190. doi:10.1111/j.1432-0436.2004.07202001.x.
- Sledz C, Holko M, de Veer M, Silverman R, Williams B. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol. 2003, 5 (9): 834–9 [2007-11-24]. PMID 12942087. (原始内容存档于2016-03-05).
外部連結
- 設計與定性工具
- Deqor: A web-based tool for the design and quality control of siRNAs
- siDirect: a web-based online software system for designing siRNA sequences (页面存档备份,存于互联网档案馆)
- siSearch: a siRNA design tool using a number of popular design methods
- SpecificityServer: a tool for checking the specificity of a given siRNA
- miRacle: tool for prediction of siRNA and microRNA targets using an algorithm which incorporates RNA secondary structure
- 数据库
- HuSiDa: Human siRNA Database (页面存档备份,存于互联网档案馆)
- siRNAdb: a database of siRNA sequences
- Nature: RNAi gateway (页面存档备份,存于互联网档案馆)
- siRNA关联企业
- Alnylam Pharmaceuticals (页面存档备份,存于互联网档案馆)
- Anadys Pharmaceuticals (页面存档备份,存于互联网档案馆)
- ArmaGen Technologies,Inc (页面存档备份,存于互联网档案馆)
- Benitec (页面存档备份,存于互联网档案馆)
- BD Biosciences (页面存档备份,存于互联网档案馆)
- Bionomics (页面存档备份,存于互联网档案馆)
- BioSpring (页面存档备份,存于互联网档案馆)
- Celera Genomics (页面存档备份,存于互联网档案馆)
- Cenix BioScience (页面存档备份,存于互联网档案馆)
- Ceptyr (页面存档备份,存于互联网档案馆)
- Finnzymes Oy (页面存档备份,存于互联网档案馆)
- Ingenium Pharmaceuticals
- Isis Pharmaceuticals
- Nucleonics Inc (页面存档备份,存于互联网档案馆)
- Pfizer Inc (页面存档备份,存于互联网档案馆)
- RNAi Co.Ltd (页面存档备份,存于互联网档案馆)
- Sigma-Aldrich (页面存档备份,存于互联网档案馆)
- Sirna Therapeutics, Inc.