Inserm U-Institut IMAGINE, Hôpital Necker-Enfants Malades, Paris, France.
Curr Gene Ther. 2012 Aug;12(4):292-300. doi: 10.2174/156652312802083602.
To date, the general assumption was that most mutations interested protein-coding genes only. Thus, only few illustrations have mentioned here that mutations may occur in non-protein coding genes such as microRNAs (miRNAs). We thus report progress in delineating their contribution as phenotypic modulators, genetic switches and fine-tuners of gene expression. We reasoned that browsing their contribution to genetic disease may provide a framework for understanding the proper requirements to devise miRNA-based therapy strategies, in particular the relief of an appropriate dosage. Gain and loss of function of miRNA enforce the need to respectively antagonize or supply the miRNAs. We further categorized human disease according to the different ways in which the miRNA was altered arising either de novo, or inherited whether as a mendelian or as an epistatic trait, uncovering its role in epigenetics. We discuss how improving our knowledge on the contribution of miRNAs to genetic disease may be beneficial to devise appropriate gene therapy strategies.
迄今为止，人们普遍认为大多数突变只影响蛋白质编码基因。因此，这里很少有说明提到突变也可能发生在非蛋白质编码基因中，如 microRNAs (miRNAs)。我们因此报告了在描述它们作为表型调节剂、遗传开关和基因表达精细调谐器的作用方面的进展。我们推断，研究它们在遗传疾病中的作用可以为理解设计基于 miRNA 的治疗策略的适当要求提供一个框架，特别是适当剂量的缓解。miRNA 的功能获得和丧失需要分别拮抗或提供 miRNA。我们还根据 miRNA 改变的不同方式对人类疾病进行了分类，这些改变要么是从头开始的，要么是遗传的，无论是孟德尔遗传还是上位遗传特征，揭示了其在表观遗传学中的作用。我们讨论了如何提高我们对 miRNA 对遗传疾病的贡献的认识，这可能有助于设计适当的基因治疗策略。
