Hennessy Erica, O'Driscoll Lorraine
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
Expert Rev Mol Med. 2008 Aug 15;10:e24. doi: 10.1017/S1462399408000781.
MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19-28 nucleotides in length. In humans, up to 3% of all genes are estimated to encode these evolutionarily conserved sequences. miRNAs are thought to control expression of thousands of target mRNAs. Mammalian miRNAs generally negatively regulate gene expression by repressing translation, possibly through effects on mRNA stability and compartmentalisation, and/or the translation process itself. An extensive range of in silico and experimental techniques have been applied to our understanding of the occurrence and functional relevance of such sequences, and antisense technologies have been successfully used to control miRNA expression in vitro and in vivo. Interestingly, miRNAs have been identified in both normal and pathological conditions, including differentiation and development, metabolism, proliferation, cell death, viral infection and cancer. Of specific relevance and excitement to the area of diabetes research, miRNA regulation has been implicated in insulin secretion from pancreatic beta-cells, diabetic heart conditions and nephropathy. Further analyses of miRNAs in vitro and in vivo will, undoubtedly, enable us determine their potential to be exploited as therapeutic targets in diabetes.
微小RNA(miRNA)是一类内源性小非编码RNA分子,长度为19 - 28个核苷酸。在人类中,估计所有基因的3%编码这些进化上保守的序列。miRNA被认为可控制数千种靶标mRNA的表达。哺乳动物的miRNA通常通过抑制翻译来负调控基因表达,可能是通过影响mRNA的稳定性和区室化,和/或翻译过程本身。广泛的计算机模拟和实验技术已被应用于我们对这类序列的发生和功能相关性的理解,并且反义技术已成功用于在体外和体内控制miRNA表达。有趣的是,在正常和病理条件下均已鉴定出miRNA,包括分化与发育、代谢、增殖、细胞死亡、病毒感染和癌症。与糖尿病研究领域特别相关且令人兴奋的是,miRNA调控已涉及胰腺β细胞的胰岛素分泌、糖尿病心脏疾病和肾病。毫无疑问,对miRNA在体外和体内的进一步分析将使我们能够确定它们作为糖尿病治疗靶点的潜在用途。