School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Key Laboratory for Computational Biology, CAS-MPG Partner Institute for Computing Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200031, China.
Biochim Biophys Acta Mol Basis Dis. 2018 Jun;1864(6 Pt B):2266-2273. doi: 10.1016/j.bbadis.2017.12.040. Epub 2018 Jan 6.
Long noncoding RNAs (lncRNAs) have been gradually emerging as important regulators in various biological processes and diseases, while the contributions of lncRNAs to atherosclerosis remain largely unknown. Our previous work has discovered atherosclerosis associated protein-coding genes by transcriptome sequencing of rabbit models. Here we investigated the roles of lncRNAs in atherosclerosis. We defined a stringent set of 3736 multi-exonic lncRNA transcripts in rabbits. All lncRNAs are firstly reported and 609 (16.3%) of them are conserved in 13 species. Rabbit lncRNAs have similar characteristics to lncRNAs in other mammals, such as relatively short length, low expression, and highly tissue-specificity. The integrative analysis of lncRNAs and co-expressed genes characterize diverse functions of lncRNAs. Comparing two kinds of atherosclerosis models (LDLR-deficient WHHL rabbits and cholesterol-fed NZW rabbits) with their corresponding controls, we found the expression changes of two rabbit models were similar in aorta in but different in liver. The shared change in aorta revealed a subset of lncRNAs involved in immune response, while the cholesterol-fed NZW rabbits showed broader lncRNA expression changes in skeletal muscle system compared to WHHL rabbits. These atherosclerosis-associated lncRNAs and genes provide hits for the experimental validation of lncRNA functions. In summary, our study systematically identified rabbit lncRNAs for the first time and provides new insights for understanding the functions of lncRNAs in atherosclerosis. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.
长链非编码 RNA（lncRNA）已逐渐成为各种生物过程和疾病的重要调控因子，而 lncRNA 对动脉粥样硬化的贡献在很大程度上仍不清楚。我们之前的工作通过兔模型的转录组测序发现了与动脉粥样硬化相关的蛋白编码基因。在这里，我们研究了 lncRNA 在动脉粥样硬化中的作用。我们在兔中定义了一套严格的 3736 个多外显子 lncRNA 转录本。所有的 lncRNA 都是首次报道的，其中 609 个（16.3%）在 13 个物种中保守。兔 lncRNA 具有与其他哺乳动物 lncRNA 相似的特征，如相对较短的长度、低表达和高度组织特异性。lncRNA 和共表达基因的综合分析描述了 lncRNA 的多种功能。比较两种动脉粥样硬化模型（LDLR 缺陷型 WHHL 兔和胆固醇喂养的 NZW 兔）与其相应的对照，我们发现两种兔模型在主动脉中的表达变化相似，但在肝脏中的变化不同。主动脉中的共同变化揭示了一组参与免疫反应的 lncRNA，而与 WHHL 兔相比，胆固醇喂养的 NZW 兔在骨骼肌系统中表现出更广泛的 lncRNA 表达变化。这些与动脉粥样硬化相关的 lncRNA 和基因为 lncRNA 功能的实验验证提供了线索。总之，我们的研究首次系统地鉴定了兔 lncRNA，并为理解 lncRNA 在动脉粥样硬化中的功能提供了新的见解。本文是由 Yudong Cai 和 Tao Huang 编辑的特刊“通过遗传和基因组大数据分析加速精准医学”的一部分。
