根据最近发表在美国《国家科学院院刊》网络版上的一项研究成果，一小段核糖核酸（RNA）能够对动物心脏造成损害。这一发现进一步证明了这类片段——例如微核糖核酸(miRNAs)——在健康与疾病中扮演了一个重要角色。
如今在动植物中已经鉴定出几百个miRNAs。尽管它们非常小——不超过基因平均长度的0.2%，但miRNAs在控制基因的表达方面却发挥着巨大作用。例如，科学家们发现，miRNAs能够调节生物的早期发育，并可能在癌症的演变过程中扮演了一个角色。虽然许多研究人员都在探索miRNAs与癌症的关系，但并未发现这些分子与其他疾病存在必然的联系。
一次偶然的机会，美国达拉斯市得克萨斯大学西南医学中心的分子生物学家Eric Olson试图搞清miRNAs是否与心脏病有关。Olson和同事首先在患有心脏病的实验室小鼠体内寻找与此有关的miRNAs表达。研究人员相继鉴定出186个不同的miRNAs，与正常的小鼠相比，其中11个miRNAs在患心脏病的小鼠中有更高的表达，而其中5个miRNAs在后者体内则有低水平的表达。高表达的5个miRNAs在采自心脏病人的心脏组织中亦有很高的表达。
为了搞清这些miRNAs是否有可能导致心脏病——而不仅仅是简单地作出反应——Olson的研究小组在小鼠体内分别过量表达了3种miRNAs。Olson回忆说：“我曾对此表示怀疑。”结果显示，当一种miRNAs的表达超过正常水平的25倍后，小鼠的心脏出现了严重的病变。此外，Olson表示，他们还在小鼠体内发现了一些类似于人类心脏病的心脏缺陷，例如心肌细胞增大等。但是这些现象的发生机制尚未搞清，研究人员还无法确定哪个基因或哪几个基因成为了miRNA的靶子。
加利福尼亚大学旧金山分校的RNA生物学家Michael McManus预测，这项研究有可能促使科学家在其他疾病领域摸清miRNAs是否也在其中扮演了一个角色。新罕布什尔州汉诺威市达特默思医学院的遗传学家Victor Ambros强调指出，这是他所知的第一项有关miRNAs与组织损伤的关系的研究。Olson的研究小组计划在这条路上走下去——他说，下一步他想搞清利用遗传手段去除miRNA是否能防止小鼠患上心脏病。
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.
