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Ambros和Ruvkun的研究始于20世纪80年代末,主要使用模式生物“秀丽隐杆线虫(C. elegans)”,一种体长仅1毫米的线虫。尽管这类生物结构简单,但其基因调控方式与复杂动物非常相似,因此成为理想的研究对象。Ambros和Ruvkun集中研究了控制线虫发育过程中基因激活时间的lin-4和lin-14两个突变基因。经过深入研究,Ambros发现,lin-4基因不编码蛋白质,而是生成了一种极其短小的RNA分子,即微小RNA(microRNA)。而Ruvkun则进一步揭示了lin-4生成的microRNA通过与lin-14基因3'UTR区域的部分序列互补,从而抑制其蛋白质的生成。
(A) C. elegans is a useful model organism for understanding how different cell types develop. (B) Ambros and Ruvkun studied the lin-4 and lin-14 mutants. Ambros had shown that lin-4 appeared to be a negative regulator of lin-14. (C) Ambros discovered that the lin-4 gene encoded a tiny RNA, microRNA, that did not code for a protein. Ruvkun cloned the lin-14 gene, and the two scientists realized that the lin-4 microRNA sequence matched a complementary sequence in the lin-14 mRNA.
Evolutionary conservation of the let-7 RNA expression and microRNAs more generally. Left: An evolutionary tree of metazoans, highlighting the branches of the tree with a detectable let-7 microRNA expression (+) or where no let-7 expression was detected (-). Species with similar developmental pattern of let-7 RNA expression is (no let-7 in early stages; but let-7 expression by adulthood) are indicated by ‘Dev.’. (Pasquinelli et al., 2000). Right: MicroRNA genes have evolved and expanded within the genomes of multicellular organisms for over 500 million years.
Ruvkun cloned let-7, a second gene encoding a microRNA. The gene is conserved in evolution, and it is now known that microRNA regulation is universal among multicellular organisms.
Victor Ambros,1953年出生于美国新罕布什尔州汉诺威。1979年从美国麻省理工学院获得博士学位,1979-1985年在麻省理工学院做博士后。他于1985年成为哈佛大学PI。1992年至2007年,他任美国达特茅斯医学院教授,目前是美国麻省大学医学院的自然科学教授。
Gary Ruvkun,1952年出生于美国加州伯克利。1982年从美国哈佛大学获得博士学位,1982年至1985年在美国麻省理工学院做博士后。他于1985年成为麻省总医院和哈佛医学院的PI,目前是遗传学教授。
【消息来源】
The Nobel Prize