Piro Rosario Michael, Marsico Annalisa
Institut für Informatik, Freie Universität Berlin, Berlin, Germany.
Institut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Methods Mol Biol. 2019;1912:301-321. doi: 10.1007/978-1-4939-8982-9_12.
The discovery that a considerable portion of eukaryotic genomes is transcribed and gives rise to long noncoding RNAs (lncRNAs) provides an important new perspective on the transcriptome and raises questions about the centrality of these lncRNAs in gene-regulatory processes and diseases. The rapidly increasing number of mechanistically investigated lncRNAs has provided evidence for distinct functional classes, such as enhancer-like lncRNAs, which modulate gene expression via chromatin looping, and noncoding competing endogenous RNAs (ceRNAs), which act as microRNA decoys. Despite great progress in the last years, the majority of lncRNAs are functionally uncharacterized and their implication for disease biogenesis and progression is unknown. Here, we summarize recent developments in lncRNA function prediction in general and lncRNA-disease associations in particular, with emphasis on in silico methods based on network analysis and on ceRNA function prediction. We believe that such computational techniques provide a valuable aid to prioritize functional lncRNAs or disease-relevant lncRNAs for targeted, experimental follow-up studies.
真核生物基因组中有相当一部分会被转录并产生长链非编码RNA(lncRNA),这一发现为转录组提供了重要的新视角,并引发了关于这些lncRNA在基因调控过程和疾病中的核心地位的问题。对lncRNA进行机制研究的数量迅速增加,这为不同的功能类别提供了证据,比如类似增强子的lncRNA,其通过染色质环化调节基因表达;以及非编码竞争性内源RNA(ceRNA),其作为微小RNA的诱饵发挥作用。尽管在过去几年取得了很大进展,但大多数lncRNA的功能尚未明确,它们在疾病发生和发展中的作用也不清楚。在这里,我们总结了lncRNA功能预测尤其是lncRNA与疾病关联方面的最新进展,重点是基于网络分析的计算机方法和ceRNA功能预测。我们认为,此类计算技术有助于优先选择功能性lncRNA或与疾病相关的lncRNA,以便进行有针对性的实验后续研究。