小干擾RNA
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小干擾RNA（Small interfering RNA；siRNA）有時(shí)稱為短干擾RNA（short interfering RNA）或沉默RNA（silencing RNA），是長度20到25個(gè)核苷酸的雙股RNA，在生物學(xué)上有許多不同的用途。目前已知siRNA主要參與RNA干擾（RNAi）現(xiàn)象，以帶有專一性的方式調(diào)節(jié)基因的表達(dá)。此外，也參與一些與RNAi相關(guān)的反應(yīng)途徑，例如抗病毒機(jī)制或是染色質(zhì)結(jié)構(gòu)的改變。不過這些復(fù)雜機(jī)制的反應(yīng)途徑目前尚未明了。
siRNA最早是由英國的大衛(wèi)·包孔博（David Baulcombe）團(tuán)隊(duì)發(fā)現(xiàn)，是植物中的后轉(zhuǎn)錄基因沉默（post-transcriptional gene silencing；PTGS）現(xiàn)象的一部分[1]，其研究結(jié)果發(fā)表于《科學(xué)》[2]。2001年，湯瑪士·涂許爾（Thomas Tuschl）團(tuán)隊(duì)發(fā)現(xiàn)合成的siRNA，可誘導(dǎo)哺乳動(dòng)物體內(nèi)的RNAi作用[3]，結(jié)果發(fā)表于《自然》[4]。這項(xiàng)發(fā)現(xiàn)引發(fā)了利用可控制的RNAi，來進(jìn)行生物醫(yī)學(xué)研究與藥物開發(fā)的方法。
目錄 |
結(jié)構(gòu)
siRNA通常是一段長21個(gè)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(gè)核苷酸，圖示如下：
每一股各有一個(gè)5'磷酸基末端與一個(gè)3'羥基末端。此結(jié)構(gòu)經(jīng)dicer作用而得，dicer這種酶將較長的雙股RNA或小發(fā)夾RNA（small hairpin RNA）切成siRNA[5]。此外，siRNA也可經(jīng)由多種不同轉(zhuǎn)染（transfection）技術(shù)導(dǎo)入細(xì)胞內(nèi)，并對特定基因產(chǎn)生具專一性的基因剔除（knockdown）效果。本質(zhì)上，任何已知序列的基因都可以、也因此是經(jīng)過適當(dāng)剪裁而具有序列互補(bǔ)性的siRNA的作用對象。這使siRNA成為研究基因功能與藥物目標(biāo)的一項(xiàng)重要工具。
參見
- 微RNA（miRNA）
參考文獻(xiàn)
- ↑ 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(jié)
- 設(shè)計(jì)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
- 數(shù)據(jù)庫：
- siRNA關(guān)聯(lián)企業(yè)
- 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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