Long non-coding RNAs: important regulators in the development, function, and disorders of the central nervous system (original) (raw)
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Neuropathology and Applied Neurobiology, 2019
Genome‐wide transcriptional studies have demonstrated that tens of thousands of long non‐coding RNAs (lncRNA) genes are expressed in the central nervous system (CNS) and that they exhibit tissue‐ and cell‐type specificity. Their regulated and dynamic expression and their co‐expression with protein‐coding gene neighbours have led to the study of the functions of lncRNAs in CNS development and disorders. In this review, we describe the general characteristics, localization and classification of lncRNAs. We also elucidate the examples of the molecular mechanisms of nuclear and cytoplasmic lncRNA actions in the CNS and discuss common experimental approaches used to identify and unveil the functions of lncRNAs. Additionally, we provide examples of lncRNA studies of cell differentiation and CNS disorders including CNS injuries and neurodegenerative diseases. Finally, we review novel lncRNA‐based therapies. Overall, this review highlights the important biological roles of lncRNAs in CNS fu...
Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders
Non-Coding RNA, 2021
Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders.
Long noncoding RNAs in development and disease of the central nervous system
Trends in Genetics, 2013
The central nervous system (CNS) is a complex biological system composed of numerous cell types working in concert. The intricate development and functioning of this highly ordered structure depends upon exquisite spatial and temporal control of gene expression in the cells comprising the CNS. Thus, gene regulatory networks that control cell fates and functions play critical roles in the CNS. Failure to develop and maintain intricate regulatory networks properly leads to impaired development or neural dysfunction, which might manifest as neurological disorders. Long noncoding RNAs (lncRNAs) are emerging as important components of gene regulatory networks, working in concert with transcription factors and epigenetic regulators of gene expression. Interestingly, many lncRNAs are highly expressed in the adult and developing brain, often showing precise temporal and spatial patterns of expression. This specificity of expression and growing awareness of the importance of lncRNAs suggest that they play key roles in CNS development and function. In this review, we highlight the growing evidence for the importance of lncRNAs in the CNS and the indications that their dysregulation underlies some neurological disorders.
Frontiers in physiology, 2014
Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs) with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation. Analysis of the genomic distribution of genes encoding for lncRNAs indicates a physical association of these regulatory RNAs with transcription factors (TFs) with well-established roles in neural differentiation, suggesting that lncRNAs and TFs may form coherent regulatory networks with important functions in neural stem cells (NSCs). Additionally, many studies show that lncRNAs are involved in the pathophysiology of brain-related diseases/disorders. Here we discuss these obs...
Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease
Frontiers in genetics, 2014
Comprehensive analysis of the mammalian transcriptome has revealed that long non-coding RNAs (lncRNAs) may make up a large fraction of cellular transcripts. Recent years have seen a surge of studies aimed at functionally characterizing the role of lncRNAs in development and disease. In this review, we discuss new findings implicating lncRNAs in controlling development of the central nervous system (CNS). The evolution of the higher vertebrate brain has been accompanied by an increase in the levels and complexities of lncRNAs expressed within the developing nervous system. Although a limited number of CNS-expressed lncRNAs are now known to modulate the activity of proteins important for neuronal differentiation, the function of the vast majority of neuronal-expressed lncRNAs is still unknown. Topics of intense current interest include the mechanism by which CNS-expressed lncRNAs might function in epigenetic and transcriptional regulation during neuronal development, and how gain and ...
Long Non-coding RNAs Associated with Brain Disorders: A Literature Review
Gene, Cell and Tissue
Context: Neurodegenerative diseases (NDs) are neurological disorders characterized by the degeneration of the central nervous system (CNS). Studies have examined interactions between long non-coding RNAs (lncRNAs) and functioning of the CNS in NDs. In this study, we summarized the role of different lncRNAs in most NDs. Methods: In this study, different papers published between years 2003 and 2020 were reviewed. Results: LncRNAs can play a significant role in the development of brain disorders. Conclusions: The dysregulation of lncRNAs has been shown to affect NDs such as Alzheimer's disease (AD) and Parkinson’s diseases (PD). In this review, we compiled recent findings related to the main lncRNAs associated with brain disorders.
Long non-coding RNAs: Diverse roles in various disorders
Human Antibodies, 2019
BACKGROUND: Long non-coding RNAs (lncRNAs) are a group of transcripts larger than 200 nucleotides that are not translated to proteins. These transcripts regulate expression of numerous genes at different levels by acting as decoys, scaffolds, and enhancers. Thus they regulate cell development, differentiation and fate. OBJECTIVE: To find the role of lncRNAs in various diseases. METHODS: We searched PubMed and google scholar and summarized the data regarding the role of lncRNAs in cancer and neurologic disorders. RESULTS: Several recent studies have shown that their expressions are up-/down-regulated in malignant tissues. Consequently, they have suggested that lncRNAs can differentiate cancer samples from normal samples. Their application as biomarker is not limited to cancers. In several neurologic or psychiatric disorders researchers have found aberrant expression of lncRNAs. CONCLUSIONS: Taken together, lncRNAs constitute a novel vast area of research to find answer to fundamental biologic questions.
Neuron, 2015
Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.