scholarly journals A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain

2018 ◽  
Author(s):  
Benjamin Kleaveland ◽  
Charlie Y. Shi ◽  
Joanna Stefano ◽  
David P. Bartel

SUMMARYNoncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.HIGHLIGHTSA long noncoding RNA, a circular RNA, and two microRNAs form a regulatory networkThe Cyrano long noncoding RNA directs potent, multiple-turnover destruction of miR-7Unchecked miR-7 prevents accumulation of Cdr1as circular RNA in cytoplasm of neurons miR-7 prevents this accumulation by enhancing the miR-671-directed slicing of Cdr1as

Epigenomics ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 1929-1947
Author(s):  
Wei Xiong ◽  
Mengran Yao ◽  
Yuqiao Yang ◽  
Yan Qu ◽  
Jinqiao Qian

Diabetic cardiovascular diseases (DCVDs) are the most common complications of diabetes mellitus and are considered to be one of the most important threats to global health and an economic burden. Long noncoding RNA (lncRNA), circular RNA (circRNA), and miRNA are a novel group of noncoding RNAs that are involved in the regulation of various pathophysiological processes, including DCVDs. Interestingly, both lncRNA and circRNA can act as competing endogenous RNA of miRNA, thereby regulating the expression of the target mRNA by decoying or sponging the miRNA. In this review, we focus on the mechanistic, pathological and functional roles of lncRNA/circRNA-miRNA-mRNA networks in DCVDs and further discuss the potential implications for early detection, therapeutic intervention and prognostic evaluation.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jen-Yang Tang ◽  
Jin-Ching Lee ◽  
Yung-Ting Chang ◽  
Ming-Feng Hou ◽  
Hurng-Wern Huang ◽  
...  

Long noncoding RNA (lncRNA) function is described in terms of related gene expressions, diseases, and cancers as well as their polymorphisms. Potential modulators of lncRNA function, including clinical drugs, natural products, and derivatives, are discussed, and bioinformatic resources are summarized. The improving knowledge of the lncRNA regulatory network has implications not only in gene expression, diseases, and cancers, but also in the development of lncRNA-based pharmacology.


Author(s):  
Xingzhe Yang ◽  
Feng Li ◽  
Jie Ma ◽  
Yan Liu ◽  
Xuejiao Wang ◽  
...  

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 251.1-251
Author(s):  
J. M. Kim ◽  
H. J. Kang ◽  
S. J. Jung ◽  
B. W. Song ◽  
H. J. Jeong ◽  
...  

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared


RSC Advances ◽  
2019 ◽  
Vol 9 (61) ◽  
pp. 35624-35635 ◽  
Author(s):  
Hui Zhao ◽  
Li Meng ◽  
Chengyang Xu ◽  
Bin Lin ◽  
Xiangming Zheng ◽  
...  

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI).


Stroke ◽  
2019 ◽  
Vol 50 (7) ◽  
pp. 1850-1858 ◽  
Author(s):  
Yiming Deng ◽  
Duanduan Chen ◽  
Luyao Wang ◽  
Feng Gao ◽  
Bo Jin ◽  
...  

Background and Purpose— Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods— We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results— We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation–treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation–induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-β–activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions— We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhou Du ◽  
Tong Sun ◽  
Ezgi Hacisuleyman ◽  
Teng Fei ◽  
Xiaodong Wang ◽  
...  

2020 ◽  
Vol 30 (05) ◽  
pp. 2050069
Author(s):  
Ming Liu ◽  
Fanwei Meng ◽  
Dongpo Hu

In this paper, the impacts of multiple time delays on a gene regulatory network mediated by small noncoding RNA is studied. By analyzing the associated characteristic equation of the corresponding linearized system, the asymptotic stability of the positive equilibrium is investigated and Hopf bifurcation is demonstrated. Furthermore, the explicit formulae for determining the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions are given by the center manifold theorem and the normal form theory for functional differential equations. Finally, some numerical simulations are demonstrated for supporting the theoretical results.


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