Akhade Vijay Suresh, Pal Debosree, Kanduri Chandrasekhar
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.
Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore, 560064, India.
Adv Exp Med Biol. 2017;1008:47-74. doi: 10.1007/978-981-10-5203-3_2.
For the last four decades, we have known that noncoding RNAs maintain critical housekeeping functions such as transcription, RNA processing, and translation. However, in the late 1990s and early 2000s, the advent of high-throughput sequencing technologies and computational tools to analyze these large sequencing datasets facilitated the discovery of thousands of small and long noncoding RNAs (lncRNAs) and their functional role in diverse biological functions. For example, lncRNAs have been shown to regulate dosage compensation, genomic imprinting, pluripotency, cell differentiation and development, immune response, etc. Here we review how lncRNAs bring about such copious functions by employing diverse mechanisms such as translational inhibition, mRNA degradation, RNA decoys, facilitating recruitment of chromatin modifiers, regulation of protein activity, regulating the availability of miRNAs by sponging mechanism, etc. In addition, we provide a detailed account of different mechanisms as well as general principles by which lncRNAs organize functionally different nuclear sub-compartments and their impact on nuclear architecture.
在过去的四十年里,我们已经知道非编码RNA维持着诸如转录、RNA加工和翻译等关键的看家功能。然而,在20世纪90年代末和21世纪初,高通量测序技术以及用于分析这些大型测序数据集的计算工具的出现,推动了数千种小非编码RNA和长非编码RNA(lncRNA)的发现及其在多种生物学功能中的作用。例如,lncRNA已被证明可调节剂量补偿、基因组印记、多能性、细胞分化与发育、免疫反应等。在这里,我们综述lncRNA如何通过多种机制发挥如此丰富的功能,如翻译抑制、mRNA降解、RNA诱饵、促进染色质修饰剂的募集、调节蛋白质活性、通过海绵机制调节miRNA的可用性等。此外,我们详细阐述了lncRNA组织功能不同的核亚区室的不同机制以及一般原则,及其对核结构的影响。