The nobel prize in physiology or medicine 2006
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The Nobel Prize in Physiology or Medicine 2006. RNAi (RNA interference). 組員:鄭詠哲 、 方 詩敏、蔡威逸、謝慧茹、呂佩璇、蘇鈺琁. 轉錄作用 轉譯作用 DNA RNA? 蛋白質 RNA 到底扮演什麼角色 ?. Andrew Z. Fire Craig C. Mello. RNAi 的發現簡史. 1990 年

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The Nobel Prize in Physiology or Medicine 2006

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The nobel prize in physiology or medicine 2006

The Nobel Prize in Physiology or Medicine 2006

RNAi (RNA interference)

組員:鄭詠哲、方詩敏、蔡威逸、謝慧茹、呂佩璇、蘇鈺琁


The nobel prize in physiology or medicine 2006

轉錄作用 轉譯作用

DNA RNA? 蛋白質

RNA到底扮演什麼角色?


Andrew z fire craig c mello

Andrew Z. Fire Craig C. Mello


The nobel prize in physiology or medicine 2006

RNAi 的發現簡史

  • 1990年

    Rich Jorgensen及A. R. Stuitji之矮牽牛花的實驗

    -共同抑制(co-suppression)

  • 1992年紅麵包黴菌(Neurospora crassa)

    -壓制(quelling)

  • 1993年菸草蝕刻病毒(Tobacco etch virus, TEV)

    -轉錄後基因靜默作用(PTGS)


Chalcone synthase

加入 chalcone synthase基因

轉殖後

or


The nobel prize in physiology or medicine 2006

  • 1998年Fire 和 Mello 線蟲實驗


Rnai r n a interference

RNAi(RNA interference)

  • 亦可稱為轉錄後基因靜默作用

    (post transcriptional gene silencing, PTGS)

    -作用有

    使mRNA降解(RNA degradation)導致

    mRNA無法作用

    抑制mRNA使其無法轉譯成蛋白質


The nobel prize in physiology or medicine 2006

a1

a2

a3

a4


The nobel prize in physiology or medicine 2006

a5

b1

b2

b3


The nobel prize in physiology or medicine 2006

b4

b5

a圖為一般蛋白質製造過程

b圖為RNAi作用的過程


The nobel prize in physiology or medicine 2006

基因默化現象

  • 區分為

    轉錄時基因默化現象

    (Transcriptional gene silencing,TGS)

    轉錄後基因默化現象

    (Post-transcriptional gene silencing,PTGS)


The nobel prize in physiology or medicine 2006

  • TGS

     將DNA甲基化使基因不表現

    直接抑制mRNA使其無法轉譯

  • PTGS

    -RNAi

  • 病毒感染引起的基因默化稱為

    Virus-induced gene silencing ,VIGS


Transposon

跳躍基因(transposon)

  • 跳躍子轉位(transposition)

    -1. 從原染色體位置跳出(excision)

    2. 跳入新的染色體位置

    Gene tagging


Sirna v s mirna

siRNA v.s miRNA

siRNA=short interfering RNA

miRNA=micro RNA

  • 最大差異

    siRNA為外源性

    miRNA為內源性 


Sirna v s mirna1

siRNA v.s miRNA

  • 相同處

    由22個左右的核苷組成

    為Dicer酶的產物

    作用時和RISC複合體結合

    干擾以抑制目標基因的轉譯


Dicer

Dicer

  • 含有RNA helicase、PAZ、RNA結合區


Risc rna induced silencing complex

RISC (RNA-induced silencing complex)

  • 含有endonuclease、exonuclease、

  • RNA helicase、重組互換蛋白質

amino-terminal

Argonaute protein


The nobel prize in physiology or medicine 2006

RNAi 的運用

  • 老年性黃斑變性(AMD)

    -視網膜上的血管異常生長,影響視力甚至

    導致失明

  • Bevasiranib

    血管內皮生長因子(VEGF)基因

抑制


The nobel prize in physiology or medicine 2006

RNAi 目前的缺點與限制

  • RNAi效能通常與siRNA的表現量相關

  • RNA易被RNAi分解為暫時狀態之表現

  • RNAi的專一性極高

  • 誘導RNAi的病毒基因片段無規則可循


The nobel prize in physiology or medicine 2006

資料來源

  • http://nobelprize.org/nobel_prizes/medicine/laureates/2006/adv.html

  • http://www.2to1agri.com/apagri/16.nsf/ByUNID/A3A3D782C276E89D4825708300219717?opendocument

  • http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html

  • http://www.ebiotrade.com/newsf/2005-8/200585101531.htm

  • http://zh.wikipedia.org/wiki/RNA%E5%B9%B2%E6%89%B0

  • http://www.rnaiweb.com/

  • http://www.qiqi8.cn/article/75/79/2007/2007031446878.html


Rnai nature

RNAi動畫圖(nature網站摘錄)

  • http://www.nature.com/focus/rnai/animations/animation/animation.htm


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