Abstract:
The central dogma of gene expression propounds that DNA is transcribed to mRNA and finally gets translated into protein. Only 2-3% of the genomic DNA is transcribed to protein-coding mRNA. Interestingly, only a further minuscule part of genomic DNA encodes for long non-coding RNAs (lncRNAs) which are characteristically more than 200 nucleotides long and can be transcribed from both protein-coding (e.g. H19 and TUG1) as well as non-coding DNA by RNA polymerase II. The lncRNAs do not have open reading frames (with some exceptions), 3`-untranslated regions (3\'-UTRs) and necessarily these RNAs lack any translation-termination regions, however, these can be spliced, capped and polyadenylated as mRNA molecules. The flexibility of lncRNAs confers them specific 3D-conformations that eventually enable the lncRNAs to interact with proteins, DNA or other RNA molecules via base pairing or by forming networks. The lncRNAs play a major role in gene regulation, cell differentiation, cancer cell invasion and metastasis and chromatin remodeling. Deregulation of lncRNA is also responsible for numerous diseases in mammals. Various studies have revealed their significance as biomarkers for prognosis and diagnosis of cancer. The aim of this review is to overview the salient features, evolution, biogenesis and biological importance of these molecules in the mammalian system.
摘要:
基因表达的中心法则提出DNA被转录为mRNA并最终被翻译成蛋白质。只有2-3%的基因组DNA被转录成编码蛋白质的mRNA。有趣的是,基因组DNA的仅另外的微小部分编码长非编码RNA(lncRNA),其特征在于长度超过200个核苷酸,并且可以通过RNA聚合酶II从蛋白质编码(例如H19和TUG1)以及非编码DNA转录。lncRNAs没有开放阅读框(有一些例外),3'-非翻译区(3'-UTR),这些RNA必然缺乏任何翻译终止区,然而,这些可以拼接,加帽和聚腺苷酸化为mRNA分子。lncRNAs的灵活性赋予它们特定的3D构象,最终使lncRNAs能够与蛋白质相互作用,DNA或其他RNA分子通过碱基配对或通过形成网络。lncRNAs在基因调控中起主要作用,细胞分化,癌细胞侵袭和转移与染色质重塑。lncRNA的失调也是哺乳动物中许多疾病的原因。各种研究已经揭示了它们作为癌症预后和诊断的生物标志物的重要性。这篇综述的目的是概述突出的特点,进化,这些分子在哺乳动物系统中的生物发生和生物学重要性。