动物长链非编码RNA研究进展

长链非编码RNA(long non-coding RNA,lncRNA)是一类广泛存在于动植物体内、长度大于200nt、基本不编码蛋白质的转录本。研究表明,lncRNA能够协助蛋白质复合体转运、参与基因和染色体的激活与失活调控等,在胚胎发育、肌肉生长、脂肪沉积以及免疫应答等过程中发挥重要作用。近年来,在人类基因组计划和ENCODE(The Encyclopedia of DNA Elements)计划推动下,在动物中不仅鉴定出数量众多的lncRNA,而且在lncRNA调控脂肪代谢、肌肉发育以及免疫抗病等重要生物学过程的机理研究方面也取得了突破性的进展。这些研究结果颠覆了lncRNA不编码蛋白的传统观念,提出了lncRNA编码功能性小肽调控生物学过程的新模型。本文主要介绍了动物lncRNA的特征与类型、常用数据库、生物学功能、分子调控模型以及未来lncRNA的研究方向,以期为动物lncRNA功能研究提供参考信息。     

长链非编码RNA研究进展

基因组计划研究表明, 在组成人类基因组的30亿个碱基对中, 仅有1.5%的核酸序列用于蛋白质编码, 其余98.5%的基因组为非蛋白质编码序列。这些序列曾被认为是在进化过程中累积的“垃圾序列”而未予以关注, 但在随后启动的ENCODE研究计划中却发现, 75%的基因组序列能够被转录成RNA, 其中近74%的转录产物为非编码RNA(Non-coding RNA, ncRNA)。在非编码RNA中, 绝大多数转录本的长度大于200个碱基, 这些“长链非编码RNA(Long non-coding RNA, lncRNA)”能够在转录及转录后水平上调节蛋白编码基因的表达, 从而广泛地参与包括细胞分化、个体发育在内的重要生命过程, 其异常表达还与多种人类重大疾病的发生密切相关。文章综述了长链非编码RNA的发现、分类、表达、作用机制以及其在个体发育和人类疾病中的作用。     

Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors

Long non-coding RNAs (lncRNAs) are a numerous class of newly discovered genes in the human genome, which have been proposed to be key regulators of biological processes, including stem cell pluripotency and neurogenesis. However, at present very little functional characterization of lncRNAs in human differentiation has been carried out. In the present study, we address this using human embryonic stem cells (hESCs) as a paradigm for pluripotency and neuronal differentiation. With a newly developed method, hESCs were robustly and efficiently differentiated into neurons, and we profiled the expression of thousands of lncRNAs using a custom-designed microarray. Some hESC-specific lncRNAs involved in pluripotency maintenance were identified, and shown to physically interact with SOX2, and PRC2 complex component, SUZ12. Using a similar approach, we identified lncRNAs required for neurogenesis. Knockdown studies indicated that loss of any of these lncRNAs blocked neurogenesis, and immunoprecipitation studies revealed physical association with REST and SUZ12. This study indicates that lncRNAs are important regulators of pluripotency and neurogenesis, and represents important evidence for an indispensable role of lncRNAs in human brain development.     

Role of long non-coding RNAs in metabolic control

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression by influencing various biological processes including proliferation, apoptosis, differentiation, and senescence. Accumulating evidence implicates lncRNAs in the maintenance of metabolic homeostasis; dysregulation of certain lncRNAs promotes the progression of metabolic disorders such as diabetes, obesity, and cardiovascular diseases. In this review, we discuss our understanding of lncRNAs implicated in metabolic control, focusing on in particular diseases arising from chronic inflammation, insulin resistance, and lipid homeostasis. We have analyzed lncRNAs and their molecular targets involved in the pathogenesis of chronic liver disease, diabetes, and obesity, and have discussed the rising interest in lncRNAs as diagnostic and therapeutic targets improving metabolic homeostasis. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen.     

Conservation analysis of long non-coding RNAs in plants

Long non-coding RNAs (lncRNAs) are gene regulators that have vital roles in development and adaptation to the environment in eukaryotes. However, the structural and evolutionary analyses of plant lncRNAs are limited. In this study, we performed an analysis of lncRNAs in five monocot and five dicot species. Our results showed that plant lncRNA genes were generally shorter and had fewer exons than protein-coding genes. The numbers of lncRNAs were positively correlated with the numbers of protein-coding genes in different plant species, despite a high range of variation. Sequence conservation analysis showed that the majority of lncRNAs had high sequence conservation at the intra-species and sub-species levels, reminiscent of protein-coding genes. At the inter-species level, a subset of lncRNAs were highly diverged at the nucleotide level, but conserved by position. Interestingly, we found that plant lncRNAs have identical splicing signals, and those which can form precursors or targets of miRNAs have a conservative identity in different species. We also revealed that most of the lowly expressed lncRNAs were tissue-specific, while those highly conserved were constitutively transcribed. Meanwhile, we characterized a subset of rice lncRNAs that were co-expressed with their adjacent protein-coding genes, suggesting they may play cis-regulatory roles. These results will contribute to understanding the biological significance and evolution of lncRNAs in plants.     

Risk stratification by long non-coding RNAs profiling in COVID-19 patients

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.     

长链非编码RNA在血液系统肿瘤中作用的研究进展

随着分子生物学技术的飞速发展,人们对于长链非编码RNA(Long non-coding RNA,lncRNA)的研究越来越深入。lncRNA不仅在生物体正常生物活动中不可或缺,还在许多疾病尤其是肿瘤中扮演重要角色。已有的研究表明多种lncRNA与血液系统肿瘤密切相关,具有影响抑癌基因p15表达、p53蛋白功能,以及与miRNA相互作用参与疾病等功能。本文综述了血液系统肿瘤相关的lncRNA并着重介绍与p15、p53、miRNA有关的lncRNA以及它们的相互作用在疾病中发挥的功能,以期能够全面了解血液系统肿瘤相关lncRNA的作用特点,为血液系统肿瘤的研究、诊断以及治疗提供新的思路。