一個(gè)國際數(shù)學(xué)家研究小組提出一種新方法來理解一個(gè)難倒分子生物學(xué)家的生物謎團(tuán),。他們利用一種數(shù)學(xué)模型來計(jì)算出一種被稱作微RNA(microRNA, miRNA)的小分子的作用機(jī)制,。
就目前而言，科學(xué)家們提出幾種不同的而且有時(shí)又相互沖突的理論來解釋miRNA調(diào)節(jié)蛋白產(chǎn)生的方式,，這是因?yàn)榧幢阒话l(fā)生微小的實(shí)驗(yàn)條件改變也會導(dǎo)致結(jié)果發(fā)生較大變化,。
來自英國萊斯特大學(xué)的Alexander Gorban教授和來自法國巴黎市居里研究所的Andrei Zinovyev與生物學(xué)者Nadya Morozova和Annick Harel-Bellan合作而構(gòu)建出一種數(shù)學(xué)模型，結(jié)果表明可能存在一種簡單的機(jī)制,，它在不同條件下作出不同的表現(xiàn),。他們的研究發(fā)現(xiàn)于2012年7月31日在線發(fā)表在RNA期刊上。
Gorban教授說，“我們發(fā)現(xiàn)看似非常不同的機(jī)制實(shí)際上一種相對簡單的生物化學(xué)反應(yīng)在不同環(huán)境下的體現(xiàn),。我們的模型提出miRNA在蛋白產(chǎn)生中可能同時(shí)發(fā)揮很多種作用,，而且根據(jù)實(shí)驗(yàn)發(fā)生的條件，它以一種穩(wěn)定而又有效率的方式發(fā)揮作用,，即調(diào)節(jié)蛋白產(chǎn)生速度,。如果這種模型被人們接受，我們將能夠采取積極的步驟來確定miRNA工作的主要機(jī)制是什么,。這將有助于解決人們在理解miRNA實(shí)際如何發(fā)揮作用的方式上已持續(xù)了十年的爭論,。”(生物谷：Bioon.com)
本文編譯自Mathematicians find solution to biological building block puzzle
doi: 10.1261/rna.032284.112
PMC:
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
