小干擾RNA
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小干擾RNA(Small interfering RNA;siRNA)有時稱為短干擾RNA(short interfering RNA)或沉默RNA(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了。
siRNA最早是由英國的大衛·包孔博(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·塗許爾(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。
目錄 |
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剔除(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。
參見
- 微RNA(miRNA)
參考文獻
- ↑ 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.
概觀:
- Hannon G, Rossi J. Unlocking the potential of the human genome with RNA interference. Nature. 2004, 431 (7006): 371-8. PMID 15372045.
- 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. PMID 11157775.
- 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.
- 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.
- 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. PMID 15619617.
- Sledz C, Williams B. RNA interference and double-stranded-RNA-activated pathways. Biochem Soc Trans. 2004, 32 (Pt 6): 952-6. PMID 15506933.
- Pebernard S, Iggo R. Determinants of interferon-stimulated gene induction by RNAi vectors. Differentiation. 2004, 72 (2-3): 103-11. PMID 15066190.
- 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. PMID 12942087.
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
- 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
- 資料庫:
- siRNA關聯企業
- Alnylam Pharmaceuticals
- Anadys Pharmaceuticals
- ArmaGen Technologies,Inc
- Benitec
- BD Biosciences
- Bionomics
- BioSpring
- Celera Genomics
- Cenix BioScience
- Ceptyr
- Finnzymes Oy
- Ingenium Pharmaceuticals
- Isis Pharmaceuticals
- Nucleonics Inc
- Pfizer Inc
- RNAi Co.Ltd
- Sigma-Aldrich
- Sirna Therapeutics, Inc.
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