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Irina V. Novikova Scott P. HennellyChang-Shung Tung Karissa Y. Sanbonmatsu 《Journal of molecular biology》2013
Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are emerging in critical aspects of gene regulation. Thousands of lncRNAs have been recently discovered in a wide range of mammalian systems, related to development, epigenetics, cancer, brain function and hereditary disease. The structural biology of these lncRNAs presents a brave new RNA world, which may contain a diverse zoo of new architectures and mechanisms. While structural studies of lncRNAs are in their infancy, we describe existing structural data for lncRNAs, as well as crystallographic studies of other RNA machines and their implications for lncRNAs. We also discuss the importance of dynamics in RNA machine mechanism. Determining commonalities between lncRNA systems will help elucidate the evolution and mechanistic role of lncRNAs in disease, creating a structural framework necessary to pursue lncRNA-based therapeutics. 相似文献
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杨蓉 《中国生物化学与分子生物学报》2017,33(5):441-447
长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度在200至数千个核苷酸序列,且不具有蛋白质编码潜能的非编码RNA。相较于研究较多的微小RNA(microRNA,miRNA)和干扰小RNA(small interfering,siRNA)等非编码小RNA,lncRNA的许多功能仍尚不清楚。但越来越多的研究发现,lncRNA可通过多种方式调控中枢神经系统发育,包括表观遗传组蛋白甲基化、转录辅因子调控、可变剪接调控等途经。而以上途经的异常均与多种人类重大疾病的发生密切相关,例如,阿尔兹海默症(Alzheimer’s disease,AD)、自闭症(autism spectrum disorder,ASD)、精神分裂症(schizophrenia,SZ)等。本文就lncRNA在表观遗传水平、转录水平、转录后水平和翻译水平上调控神经系统发育以及其在人类神经性疾病中的作用进行综述。 相似文献
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Zheng Li Xingye Li Xin Chen Shugang Li Idy H. T. Ho Xiaodong Liu Matthew T. V. Chan William K. K. Wu 《Cell proliferation》2019,52(1)
Neuropathic pain, a type of chronic and potentially disabling pain resulting from primary injury/dysfunction of the somatosensory nervous system and spinal cord injury, is one of the most intense types of chronic pain, which incurs a significant economic and public health burden. However, our understanding of its cellular and molecular pathogenesis is still far from complete. Long non‐coding RNAs (lncRNAs) are important regulators of gene expression and have recently been characterized as key modulators of neuronal functions. Emerging evidence suggested that lncRNAs are deregulated and play pivotal roles in the development of neuropathic pain. This review summarizes the current knowledge about the roles of deregulated lncRNAs (eg, KCNA2‐AS, uc.48+, NONRATT021972, MRAK009713, XIST, CCAT1) in the development of neuropathic pain. These studies suggested that specific regulation of lncRNAs or their downstream targets might provide novel therapeutic avenues for this refractory disease. 相似文献
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Identification and analysis of a key long non‐coding RNAs (lncRNAs)‐associated module reveal functional lncRNAs in cardiac hypertrophy
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Bo Ai Xuefeng Bai Yuejuan Liu Xuecang Li Jianmei Zhao Shengshu Shi Xin Chen Xiaojie Su Chunquan Li 《Journal of cellular and molecular medicine》2018,22(2):892-903
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JianWei Li Cheng Gao YuChen Wang Wei Ma Jian Tu JunPei Wang ZhenZhen Chen Wei Kong QingHua Cui 《中国科学:生命科学英文版》2014,57(8):852-857
Long noncoding RNAs (lncRNAs) play important roles in human diseases including vascular disease. Given the large number of lncRNAs, however, whether the majority of them are associated with vascular disease remains unknown. For this purpose, here we present a genomic location based bioinformatics method to predict the lncRNAs associated with vascular disease. We applied the presented method to globally screen the human lncRNAs potentially involved in vascular disease. As a result, we predicted 3043 putative vascular disease associated lncRNAs. To test the accuracy of the method, we selected 10 lncRNAs predicted to be implicated in proliferation and migration of vascular smooth muscle cells (VSMCs) for further experimental validation. The results confirmed that eight of the 10 lncRNAs (80%) are validated. This result suggests that the presented method has a reliable prediction performance. Finally, the presented bioinformatics method and the predicted vascular disease associated lncRNAs together may provide helps for not only better understanding of the roles of lncRNAs in vascular disease but also the identification of novel molecules for the diagnosis and therapy of vascular disease. 相似文献
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Triple‐negative breast cancer (TNBC) is a type of breast cancer that has a higher risk of distant recurrence and metastasis, leading to a relatively aggressive biological behaviour and poor outcome. So far, the clinical management of TNBC is challenging because of its heterogeneity and paucity of specific targeted therapy. Recently, various studies have identified a lot of differently expressed long non‐coding RNAs (lncRNAs) in TNBC. Those lncRNAs have been reported to play important roles in the multistep process of TNBC tumorigenesis. Here, we review the biological characteristics of lncRNAs, and present the current state of knowledge concerning the expression, function and regulation of lncRNAs in TNBC. Accumulating studies explored the potential lncRNAs‐based therapeutics in TNBC, including the techniques of genetic modification using antisense oligonucleotides, locked nucleic acid and RNA nanotechnology. In current review, we also discuss the future prospects of studies about lncRNAs in TNBC and development of lncRNA‐based strategies for clinical TNBC patients. 相似文献
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Yixin Xie Min Wang Jingjing Tian Xianping Li Min Yang Kan Zhang Shan Tan Lingli Luo Can Luo Longkai Peng Aiguo Tang 《Journal of cellular and molecular medicine》2019,23(10):6530-6542
Advances in microarray, RNA‐seq and omics techniques, thousands of long non‐coding RNAs (lncRNAs) with unknown functions have been discovered. LncRNAs have presented a diverse perspective on gene regulation in diverse biological processes, especially in human immune response. Macrophages participate in the whole phase of immune inflammatory response. They are able to shape their phenotype and arouse extensive functional activation after receiving physiological and pathological stimuli. Emerging studies indicated that lncRNAs participated in the gene regulatory network during complex biological processes of macrophage, including macrophage‐induced inflammatory responses. Here, we reviewed the existing knowledges of lncRNAs in the processes of macrophage development and polarization, and their roles in several different inflammatory diseases. Specifically, we focused on how lncRNAs function in macrophage, which might help to discover some potential therapeutic targets and diagnostic biomarkers. 相似文献
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LncRNA调控骨骼肌发育的分子机制及其在家养动物中的研究进展 总被引:2,自引:0,他引:2
骨骼肌是维持机体功能必不可少的组织,与家养动物的产肉率等重要经济性状密切相关。近年来,高通量测序鉴定了大量与骨骼肌生成相关的长链非编码RNA (long non-coding RNA, lncRNA),它们可作为调节因子在表观调控、转录调控以及转录后调控等多个层面调控基因表达。lncRNA通过靶向关键因子参与调控骨骼肌发育的各个环节,包括骨骼肌干细胞增殖、迁移、分化,成肌细胞增殖、分化、肌管融合,肌纤维肥大和纤维类型转换等过程。本文重点归纳了lncRNA在人和小鼠骨骼肌发育中的分子调控机制,介绍了lncRNA的研究方法,综述了lncRNA在家养动物骨骼肌发育中的研究进展,分析了目前家养动物lncRNA研究所面临的困难和挑战,最后展望了未来家养动物lncRNA研究的方向,以期为进一步阐明骨骼肌生长发育的分子调控机制提供参考。 相似文献
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lncRNAs功能注释和预测 总被引:1,自引:0,他引:1
随着测序技术的发展,在各种哺乳动物中发现越来越多的长非编码RNAs(long non-coding RNAs,lncRNAs),但是大部分lncRNAs的功能却未知.鉴于lncRNAs在众多生物过程如免疫反应、发育和基因印迹中表现出对蛋白编码基因和其它非编码RNAs的重要调节作用,对lncRNAs的功能研究也成为生物学家和生物信息学家研究的热点. 其中,功能注释和预测是目前研究lncRNAs功能的主要方法之一.本文主要对lncRNAs功能注释和预测方法的研究进展作一综述,包括以下几个方面:基于共表达网络的方法、基于miRNAs的方法、基于蛋白质结合的方法、基于表观遗传修饰的方法以及基于ceRNA网络的方法. 为进一步研究lncRNAs的功能提供参考,同时为开发更加有效的注释或预测方法提供线索. 相似文献
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Nonthaphat Kent Wong Chien-Ling Huang Rashidul Islam Shea Ping Yip 《Journal of hematology & oncology》2018,11(1):131
Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs. 相似文献
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Nanxi Yu Hongran Qin Fangxiao Zhang Tingting Liu Kun Cao Yanyong Yang Yuanyuan Chen Jianming Cai 《The journal of gene medicine》2023,25(3):e3470
DNA double-strand breaks can seriously damage the genetic information that organisms depend on for survival and reproduction. Therefore, cells require a robust DNA damage response mechanism to repair the damaged DNA. Homologous recombination (HR) allows error-free repair, which is key to maintaining genomic integrity. Long non-coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides. In recent years, a number of studies have found that lncRNAs can act as regulators of gene expression and DNA damage response mechanisms, including HR repair. Moreover, they have significant effects on the occurrence, development, invasion and metastasis of tumor cells, as well as the sensitivity of tumors to radiotherapy and chemotherapy. These studies have therefore begun to expose the great potential of lncRNAs for clinical applications. In this review, we focus on the regulatory roles of lncRNAs in HR repair. 相似文献
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Manli Yu Xinghua Shan Yu Liu Jiaqi Zhu Qingxin Cao Fan Yang Yang Liu Guokun Wang Xianxian Zhao 《Journal of cellular biochemistry》2019,120(10):18278-18287
Hyperglycemia in diabetic patients would cause cardiomyocytes oxidative stress and apoptosis due to the excessive reactive oxygen species (ROS) accumulation, leading to progressive deterioration of cardiac structure and function. Long noncoding RNAs (lncRNAs) play essential roles on controlling oxidative stress and apoptotic activity. In the present study, RNA sequencing was used to detect the differentially expressed lncRNAs during high glucose-induced cardiomyocytes oxidative stress and apoptosis. A total of 306/400 lncRNAs were identified as differentially expressed, including 156/198 lncRNAs with increased expression and 150/202 lncRNAs with decreased expression at 24 hours/48 hours after high-glucose stimulation respectively. Among these dysregulated lncRNAs, 45 lncRNAs were consistently differentially expressed in cardiomyocytes at both two time points after high-glucose stimulation. Twenty lncRNAs were upregulated and 25 lncRNAs were downregulated at both 24 hours and 48 hours, respectively. The top three upregulated lncRNAs, NONRATT029805.2, NONRATT007560.2, and NONRATT002486.2 were selected for functional studies to determine the role in oxidative stress-related apoptosis. The results showed that inhibition of non-ratt007560.2 could abate the formation of ROS and reduce apoptosis, suggesting NONRATT007560.2 might play critical roles in the development of cardiomyopathy. The dysregulated lncRNAs might participate in regulating cardiomyocytes oxidative stress and apoptosis. These findings would be important theoretical and experimental basis for investigation on diabetic cardiomyopathy pathogenesis 相似文献
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