微RNA（miRNAs）,、即被認(rèn)為通過(guò)對(duì)基因表達(dá)的影響參與很多生物過(guò)程的非編碼RNA的發(fā)現(xiàn),，正在改變我們對(duì)基因被調(diào)控的方式的認(rèn)識(shí)。我們對(duì)它們?cè)诓溉閯?dòng)物活體中的功能知之甚少,，但新開(kāi)發(fā)的一組能使小鼠的miRNA沉寂的化合物,，可為研究它們的功能提供一個(gè)強(qiáng)大的工具，也可為使患者的miRNA沉寂提供一個(gè)潛在的治療策略,。被稱為“antagomirs”的這些新試劑是通過(guò)化學(xué)方法合成的寡核苷酸,，具有與天然miRNA形成互補(bǔ)的序列。對(duì)小鼠靜脈注射拮抗miR-16,、-122、-192 和 -194的“antagomirs”,，會(huì)使肝臟,、肺臟、腎臟,、心臟,、小腸、脂肪,、皮膚,、骨髓、肌肉,、卵巢和腎上腺等中的相應(yīng)的miRNA明顯減少,。（Letter p. 685）在蠕蟲(chóng)和蒼蠅中，miRNA在胚胎中具有重要的發(fā)育作用,。在脊椎動(dòng)物中,，各種不同的發(fā)育基因被發(fā)現(xiàn)是miRNA調(diào)控的直接目標(biāo)，但此前還沒(méi)有miRNA在已知的發(fā)育過(guò)程中起特定作用的例子?，F(xiàn)在,，這樣一個(gè)例子已經(jīng)被找到：miR196在小鼠胚胎中起一個(gè)防故障裝置的作用，用來(lái)確保主要由Hoxb8 和 Shh轉(zhuǎn)錄因子調(diào)控的基因的準(zhǔn)確表達(dá),。這一結(jié)果支持認(rèn)為很多脊椎動(dòng)物的miRNA的功能可能是二級(jí)基因調(diào)控的觀點(diǎn),。
a, Sequence of the 3' UTR of Hoxb8 complements miR-196. An arrow indicates the 5' end of the primary cleavage product. b, 5' RACE analysis in hindlimb and forelimb. Of the 96 hindlimb clones sequenced, 33 yielded a sequence consistent with miR-196-directed cleavage (red); four were also truncated Hoxb8 clones, but cleavage was outside the miRNA-binding site (pink); and 59 were sequences unrelated to Hoxb8 (blue). In the forelimb, no clones were consistent with miR-196-directed cleavage. c, By whole-mount in situ hybridization with a Hoxb8 probe, an expression domain of Hoxb8 was detected in the forelimb field (red bars), but not in the hindlimb field (green bars), of a stage-16 chick embryo (n = 8/8). d, Early pan infection with RCAS::miR-196 resulted in downregulation of Hoxb8 (n = 6/6). e, An RA-soaked bead implanted into the anterior aspect of a stage-22 wild-type forelimb induced Hoxb8 expression (n = 8/10). f, Only marginal induction of Hoxb8 expression was detected on implantation of an RA-soaked bead in a forelimb infected with RCAS::miR-196 (n = 6/8). Anterior view; D, dorsal; V, ventral.
原始出處：
Eran Hornstein, Jennifer H. Mansfield, Soraya Yekta, Jimmy Kuang-Hsien Hu, Brian D. Harfe, Michael T. McManus, Scott Baskerville, David P. Bartel and Clifford J. Tabin. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development,Nature 438, 671-674
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MiRNA知識(shí)介紹
在遺傳學(xué), miRNA (微核糖核酸) 是長(zhǎng)期以來(lái)是典型地20-25 核苷酸唯一擱淺的核糖核酸的形式, 和被認(rèn)為調(diào)控miRNAs 是核糖核酸基因被抄錄從DNA, 但不被翻譯成蛋白質(zhì)其它基因的表示。對(duì)miRNA 基因比miRNA 編碼是更長(zhǎng)的DNA 序列,。這個(gè)DNA 序列包括miRNA 序列和近似反向補(bǔ)全,。當(dāng)這個(gè)DNA 序列被抄錄成一個(gè)唯一擱淺的核糖核酸分子、miRNA 序列和其反向補(bǔ)全基地對(duì)形成一個(gè)雙重?cái)R淺的核糖核酸簪子圈; 這形成一個(gè)主要miRNA 結(jié)構(gòu)(pri-miRNA) ,。Drosha, 核酵素, 劈開(kāi)簪子的基地形成pre-miRNA ,。Pre-miRNA 分子活躍地然后被運(yùn)輸入中堅(jiān)力量由Exportin 5, 載體蛋白質(zhì)。Dicer 酵素然后裁減20-25 核苷酸從簪子的基地發(fā)行成熟miRNA ,。
MiRNAs 的作用看來(lái)是在基因章程,。為那個(gè)目的, miRNA 是補(bǔ)全對(duì)部份的一個(gè)或更多信使RNAs (mRNAs), 通常在一個(gè)站點(diǎn)在3' UTR ,。MiRNA 的燜火對(duì)mRNA 禁止蛋白質(zhì)翻譯。在某些情況下, double-stranded 核糖核酸的成立通過(guò)miRNA 的捆綁觸發(fā)mRNA 抄本的退化通過(guò)過(guò)程相似與核糖核酸干涉(RNAi), 雖則在它被相信的其它案件miRNA 復(fù)合體阻攔蛋白質(zhì)翻譯機(jī)械或否則防止蛋白質(zhì)翻譯沒(méi)有導(dǎo)致mRNA 被貶低,。
1993 年這個(gè)作用第一次被描述了為 蠕蟲(chóng) Caenorhabditis elegans 由R. C. 李哈佛大學(xué),。2002 年自, miRNAs 被證實(shí)了以各種各樣的植物和動(dòng)物, 包括 C. elegans、人和工廠 Arabidopsis thaliana,?；虮话l(fā)現(xiàn)了在是相似在感覺(jué)的細(xì)菌他們控制mRNA 豐盈或翻譯由束縛mRNA 由基本配對(duì), 然而他們一般不認(rèn)為是miRNAs 因?yàn)镈icer 酵素不是包含的。
條款 miRNA 第一次被介紹了在一套三項(xiàng)條款在科學(xué)(2001 十月26 日)
在工廠中, 所謂的 siRNAs 使用防止病毒核糖核酸的副本,。然而這siRNA double-stranded, 機(jī)制似乎緊密地與那miRNA 相關(guān), 特別是采取簪子結(jié)構(gòu)入帳戶siRNAs 并且被利用調(diào)控多孔的基因, 如同miRNAs ,。
參考
本文定義miRNA 和提出指南隨后而來(lái)在分類核糖核酸基因作為miRNA 。勝者Ambros, 健美的Bartel, 大衛(wèi)P. Bartel, 克里斯托弗·B. Burge, 詹姆斯·C. Carrington, Xuemei Chenand, Gideon ·Dreyfuss, 夏恩·R. Eddy, Sam ·Griffiths 瓊斯, Mhairi 馬歇爾, Marjori Matzke, 加利Ruvkun 和托馬斯·Tuschl (2003)"一個(gè)一致的系統(tǒng)為microRNA 注釋", 核糖核酸, 9: 277-279 ,。 鏈接 本文討論miRNA 和siRNAs 被介入的過(guò)程, 就2 項(xiàng)條款狀況在學(xué)報(bào)科學(xué)的同樣問(wèn)題 ,。大衛(wèi)Baulcombe (2002)"核糖核酸微觀世界", 科學(xué), 297: 2002-2003 。 鏈接 本文描述在林的 發(fā)現(xiàn)4 上, 第一miRNA 被發(fā)現(xiàn)(編者按: 實(shí)際上, Wikipedia 編輯未讀本文, 只有做的推斷從傳票) ,。李,、R.C. 、Feinbaum ,、R.L. 和Ambros, V. (1993)" C. elegans heterochronic 基因 林4 輸入小RNAs 以antisense 互補(bǔ)性對(duì) 林14", 細(xì)胞, 75: 843854. 鏈接
相關(guān)報(bào)道：
基礎(chǔ)知識(shí)
·什么是miRNAs?
·miRNA:一種新的基因表達(dá)調(diào)節(jié)子
·miRNA是一類小分子RNA
·miRNA作用機(jī)理圖
實(shí)驗(yàn)方法
·從小鼠和人中克隆miRNA實(shí)驗(yàn)方法
·新方法分析miRNA和siRNA
·miRNA和siRNA的實(shí)驗(yàn)方法[麻省]
·miRNA & siRNA的檢測(cè)
調(diào)控與疾病
·miRNA的組織特異性調(diào)控
·PNAS:發(fā)現(xiàn)miRNA在調(diào)節(jié)卵生長(zhǎng)過(guò)程中的重要作用
·miRNA的生物起源與癌癥
·miRNA表達(dá)芯片揭示癌癥基因
·皰疹病毒家族miRNA的鑒別
·研究發(fā)現(xiàn)能檢測(cè)慢性淋巴白血病的miRNA基因
·果蠅中miRNA像原癌基因一樣
·調(diào)節(jié)控制葉子形狀基因
·miRNA mir1與細(xì)胞快速生長(zhǎng)
·植物miRNA功能研究有新發(fā)現(xiàn)
·Nature:miRNA給糖尿病患者帶來(lái)希望
·ime to grow up: the temporal role of smallRN...
·cience:妥瑞癥遺傳基因SLITRK1存在miRNA調(diào)控機(jī)制
·solate It All:siRNA miRNA Total RNA Native Pr...
·miRNA調(diào)節(jié)造血干細(xì)胞分化
·miRNA-23控制神經(jīng)元的分化
·王曉東最新Cell文章深度解析RNAi
通訊作者實(shí)驗(yàn)室介紹：
Harvard Medical School
New Research Building, 3rd Floor
77 Avenue Louis Pasteur
Boston MA 02115
Tel: (617) 432-7618
Fax: (617) 432-7595
Email: [email protected]
8 postdoctoral fellows, 5 graduate students
The laboratory studies the genetic basis by which form and structure are regulated during vertebrate development. We combine classical methods of experimental embryology with modern molecular and genetic techniques for regulating gene expression during embryogenesis.
One of the classic systems for the study of embryonic development is the chick embryo, where grafting experiments have given profound insight into such questions as the patterning of developing limb axes, and the control of organogenesis. These classical experiments provide a context for interpreting modern molecular studies and the methods they employed also give us an additional set of tools for manipulating the embryo. For example, we can use retroviral vectors to alter gene expression in the context of specific transplantations or extirpations. Important complementary information is gained from studies taking advantage of the powerful techniques for regulated misexpression and gene deletion in the mouse.
The lab has major efforts underway exploiting these approaches to understand limb development, from the establishment of the initial axes, to understanding the difference in genetic controls between an arm and a leg, through later specific events such as differential bone growth and specific muscle patterning; and to understand the establishment of left-right asymmetry (e.g.. why your heart is on the left and not the right) from the initiation of the left-right difference, through signaling cascades, to left- or right-specific morphogenesis. We also currently have projects looking at the differentiation of the somites and morphogenesis of the heart, as well as biochemical analysis of the hedgehog signal transduction system, a key signaling pathway during development. In addition, we have evolutionary projects examining the developmental and genetic basis for the morphological variation seen in Darwin's Finches and in cave fish.
References:
Kardon, G., Harfe, B. and Tabin, CJ., ?A Tcf4-Positive Mesodermal Population Provides a Prepattern for Vertebrate Limb Muscle Patterning. Developmental Cell 2003, December;5:937-944
Harfe, BD., Scherz, PJ., Nissim, S., Tian, H., McMahon, AP. and Tabin, CJ. ?Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 2004, August;118(4):517-528
Abzhanov, A., Protas, M., Grant, R., Grant, P. and Tabin, CJ. Bmp4 and morphological variation of the beaks of Darwin's Finches. Science 2004, September;305(5689):1462-1465
