Nervi Clara, Grignani Francesco
Department of Medical-Surgical Sciences and Biotechnologies, University "La Sapienza", Rome, Italy,
Subcell Biochem. 2014;70:151-79. doi: 10.1007/978-94-017-9050-5_8.
MicroRNA MicroRNA s (miRNAs) are small noncoding RNAs acting as endogenous regulators of gene expression. Their discovery is one of the major recent breakthroughs in molecular biology. miRNAs establish a multiplicity of relationships with target mRNAs and exert pleiotropic biological effects in many cell physiological pathways during development and adult life. The dynamic nature of gene expression regulation by Retinoic Acid Retinoic acid (RA) is consistent with an extensive functional interplay with miRNA activities. In fact, RA regulates the expression of many different miRNAs, thus suggesting a relevant function of miRNAs in RA-controlled gene expression programmes. miRNAs have been extensively studied as targets and mediators of the biological activity of RA during embryonic development as well as in normal and neoplastic cells. However, relatively few studies have experimentally explored the direct contribution of miRNA function to the RA signalling pathway. Here, we provide an overview of the mechanistic aspects that allow miRNA biogenesis, functional activation and regulation, focusing on recent evidence that highlights a functional interplay between miRNAs and RA-regulated molecular networks. We report examples of tissue-specific roles of miRNAs modulated by RA in stem cell pluripotency maintenance and regeneration, embryonic development, hematopoietic and neural differentiation, and other biological model systems, underlining their role in disease pathogenesis. We also address novel areas of research linking the RA signalling pathway to the nuclear activity of miRNAs.
微小RNA（miRNA）是一类小的非编码RNA，作为基因表达的内源性调节因子发挥作用。它们的发现是分子生物学领域近期的重大突破之一。miRNA与靶mRNA建立了多种关系，并在发育和成年期的许多细胞生理途径中发挥多效性生物学作用。视黄酸（RA）对基因表达的动态调节性质与miRNA活性存在广泛的功能相互作用相一致。事实上，RA调节许多不同miRNA的表达，这表明miRNA在RA控制的基因表达程序中具有重要功能。在胚胎发育以及正常和肿瘤细胞中，miRNA作为RA生物活性的靶点和介质已被广泛研究。然而，相对较少的研究通过实验探索了miRNA功能对RA信号通路的直接贡献。在这里，我们概述了允许miRNA生物合成、功能激活和调节的机制方面，重点关注突出miRNA与RA调节的分子网络之间功能相互作用的最新证据。我们报告了RA调节的miRNA在干细胞多能性维持和再生、胚胎发育、造血和神经分化以及其他生物模型系统中的组织特异性作用实例，强调了它们在疾病发病机制中的作用。我们还探讨了将RA信号通路与miRNA核活性联系起来的新研究领域。
