根據(jù)最近發(fā)表在美國(guó)《國(guó)家科學(xué)院院刊》網(wǎng)絡(luò)版上的一項(xiàng)研究成果,，一小段核糖核酸（RNA）能夠?qū)?dòng)物心臟造成損害。這一發(fā)現(xiàn)進(jìn)一步證明了這類片段——例如微核糖核酸(miRNAs)——在健康與疾病中扮演了一個(gè)重要角色,。
如今在動(dòng)植物中已經(jīng)鑒定出幾百個(gè)miRNAs,。盡管它們非常小——不超過(guò)基因平均長(zhǎng)度的0.2%，但miRNAs在控制基因的表達(dá)方面卻發(fā)揮著巨大作用,。例如,，科學(xué)家們發(fā)現(xiàn)，miRNAs能夠調(diào)節(jié)生物的早期發(fā)育,，并可能在癌癥的演變過(guò)程中扮演了一個(gè)角色,。雖然許多研究人員都在探索miRNAs與癌癥的關(guān)系，但并未發(fā)現(xiàn)這些分子與其他疾病存在必然的聯(lián)系,。
一次偶然的機(jī)會(huì),，美國(guó)達(dá)拉斯市得克薩斯大學(xué)西南醫(yī)學(xué)中心的分子生物學(xué)家Eric Olson試圖搞清miRNAs是否與心臟病有關(guān)。Olson和同事首先在患有心臟病的實(shí)驗(yàn)室小鼠體內(nèi)尋找與此有關(guān)的miRNAs表達(dá),。研究人員相繼鑒定出186個(gè)不同的miRNAs,，與正常的小鼠相比，其中11個(gè)miRNAs在患心臟病的小鼠中有更高的表達(dá),，而其中5個(gè)miRNAs在后者體內(nèi)則有低水平的表達(dá),。高表達(dá)的5個(gè)miRNAs在采自心臟病人的心臟組織中亦有很高的表達(dá)。
為了搞清這些miRNAs是否有可能導(dǎo)致心臟病——而不僅僅是簡(jiǎn)單地作出反應(yīng)——Olson的研究小組在小鼠體內(nèi)分別過(guò)量表達(dá)了3種miRNAs,。Olson回憶說(shuō)：“我曾對(duì)此表示懷疑。”結(jié)果顯示,，當(dāng)一種miRNAs的表達(dá)超過(guò)正常水平的25倍后,，小鼠的心臟出現(xiàn)了嚴(yán)重的病變,。此外，Olson表示,，他們還在小鼠體內(nèi)發(fā)現(xiàn)了一些類似于人類心臟病的心臟缺陷，例如心肌細(xì)胞增大等,。但是這些現(xiàn)象的發(fā)生機(jī)制尚未搞清,，研究人員還無(wú)法確定哪個(gè)基因或哪幾個(gè)基因成為了miRNA的靶子。
加利福尼亞大學(xué)舊金山分校的RNA生物學(xué)家Michael McManus預(yù)測(cè),，這項(xiàng)研究有可能促使科學(xué)家在其他疾病領(lǐng)域摸清miRNAs是否也在其中扮演了一個(gè)角色,。新罕布什爾州漢諾威市達(dá)特默思醫(yī)學(xué)院的遺傳學(xué)家Victor Ambros強(qiáng)調(diào)指出，這是他所知的第一項(xiàng)有關(guān)miRNAs與組織損傷的關(guān)系的研究,。Olson的研究小組計(jì)劃在這條路上走下去——他說(shuō),，下一步他想搞清利用遺傳手段去除miRNA是否能防止小鼠患上心臟病。
英文原文：
Small Molecule, Big Threat
A tiny sliver of RNA can destroy an animal's heart, according to research published online this week in Proceedings of the National Academy of Sciences. The finding boosts evidence that such fragments--known as microRNAs (miRNAs)--play important roles in health and disease.
Hundreds of miRNAs have been identified in plants and animals. Despite their tiny size--less than 0.2% the length of the average gene--miRNAs exert a powerful amount of control on gene expression (ScienceNOW, 19 January 2005). Scientists have found that miRNAs regulate early development, for example, and may play a role in cancer progression. But while more and more researchers are exploring the link between miRNAs and cancer, the molecules haven't been publicly tied to other diseases.
On a lark, molecular biologist Eric Olson of the University of Texas Southwestern Medical Center in Dallas set out to learn whether any miRNAs were involved in stressed-out hearts. First, Olson and colleagues looked for expression of miRNAs in heart tissue from mice with experimentally induced heart failure. The team identified 186 different miRNAs, 11 of which were more highly expressed in the unhealthy mice than in normal mice, and five of which were expressed at lower levels than in normal mice. Five of the miRNAs with higher expression were also found in unusually high quantities in heart tissue collected from people with heart failure.
To see whether some of these miRNAs could cause heart failure--as opposed to simply reacting to it--Olson's team overexpressed three of the miRNAs, separately, in mice. "I was skeptical," Olson recalls. Yet one did indeed leave mice with severely abnormal hearts when overexpressed at levels 25 times those found in normal animals. What's more, the heart defects resembled defects seen in humans with heart failure, in which cardiac muscle cells stretch in size, says Olson. But it's not clear how this is happening; the researchers haven't yet determined which gene or genes the miRNA targets.
Michael McManus, an RNA biologist at the University of California, San Francisco, predicts that the work may prompt scientists in other disease areas to examine whether miRNAs have a role there. Victor Ambros, a geneticist at Dartmouth Medical School in Hanover, New Hampshire, notes that this is one of the first studies he's seen that hunts for links between miRNAs and tissue trauma. Olson's team plans to continue down this path--in particular, he says, he wonders whether genetically erasing the miRNA that prompted heart failure in mice can prevent it.
