一个国际数学家研究小组提出一种新方法来理解一个难倒分子生物学家的生物谜团。他们利用一种数学模型来计算出一种被称作微RNA(microRNA, miRNA)的小分子的作用机制。
就目前而言，科学家们提出几种不同的而且有时又相互冲突的理论来解释miRNA调节蛋白产生的方式，这是因为即便只发生微小的实验条件改变也会导致结果发生较大变化。
来自英国莱斯特大学的Alexander Gorban教授和来自法国巴黎市居里研究所的Andrei Zinovyev与生物学者Nadya Morozova和Annick Harel-Bellan合作而构建出一种数学模型，结果表明可能存在一种简单的机制，它在不同条件下作出不同的表现。他们的研究发现于2012年7月31日在线发表在RNA期刊上。
Gorban教授说，“我们发现看似非常不同的机制实际上一种相对简单的生物化学反应在不同环境下的体现。我们的模型提出miRNA在蛋白产生中可能同时发挥很多种作用，而且根据实验发生的条件，它以一种稳定而又有效率的方式发挥作用，即调节蛋白产生速度。如果这种模型被人们接受，我们将能够采取积极的步骤来确定miRNA工作的主要机制是什么。这将有助于解决人们在理解miRNA实际如何发挥作用的方式上已持续了十年的争论。”(生物谷：Bioon.com)
本文编译自Mathematicians find solution to biological building block puzzle
doi: 10.1261/rna.032284.112
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PMID:
Kinetic signatures of microRNA modes of action
Nadya Morozova1,2,7, Andrei Zinovyev3,4,5,7, Nora Nonne1,2, Linda-Louise Pritchard1,2, Alexander N. Gorban6 and Annick Harel-Bellan
MicroRNAs (miRNAs) are key regulators of all important biological processes, including development, differentiation, and cancer. Although remarkable progress has been made in deciphering the mechanisms used by miRNAs to regulate translation, many contradictory findings have been published that stimulate active debate in this field. Here we contribute to this discussion in three ways. First, based on a comprehensive analysis of the existing literature, we hypothesize a model in which all proposed mechanisms of microRNA action coexist, and where the apparent mechanism that is detected in a given experiment is determined by the relative values of the intrinsic characteristics of the target mRNAs and associated biological processes. Among several coexisting miRNA mechanisms, the one that will effectively be measurable is that which acts on or changes the sensitive parameters of the translation process. Second, we have created a mathematical model that combines nine known mechanisms of miRNA action and estimated the model parameters from the literature. Third, based on the mathematical modeling, we have developed a computational tool for discriminating among different possible individual mechanisms of miRNA action based on translation kinetics data that can be experimentally measured (kinetic signatures). To confirm the discriminatory power of these kinetic signatures and to test our hypothesis, we have performed several computational experiments with the model in which we simulated the coexistence of several miRNA action mechanisms in the context of variable parameter values of the translation
