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      Long noncoding RNAs in neurodevelopment and Parkinson’s disease

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          Abstract

          Long noncoding RNAs (lncRNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lncRNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post‐transcriptional levels. Here, we review the role of lncRNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson's disease (PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lncRNA‐based disease diagnosis and drug treatment for PD.

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          Most cited references82

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          RNA maps reveal new RNA classes and a possible function for pervasive transcription.

          Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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            The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis.

            Long noncoding RNAs (lncRNAs) are abundant in the mammalian transcriptome, and many are specifically expressed in the brain. We have identified a group of lncRNAs, including rhabdomyosarcoma 2-associated transcript (RMST), which are indispensable for neurogenesis. Here, we provide mechanistic insight into the role of human RMST in modulating neurogenesis. RMST expression is specific to the brain, regulated by the transcriptional repressor REST, and increases during neuronal differentiation, indicating a role in neurogenesis. RMST physically interacts with SOX2, a transcription factor known to regulate neural fate. RMST and SOX2 coregulate a large pool of downstream genes implicated in neurogenesis. Through RNA interference and genome-wide SOX2 binding studies, we found that RMST is required for the binding of SOX2 to promoter regions of neurogenic transcription factors. These results establish the role of RMST as a transcriptional coregulator of SOX2 and a key player in the regulation of neural stem cell fate. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Long non-coding RNA: Classification, biogenesis and functions in blood cells

              While there exist some long non-coding RNAs (lncRNAs) that are structurally similar to mRNAs (capped, spliced, poly a tail), not all of the lncRNAs exhibit these features. Structurally, lncRNAs are classified under the regulatory non-coding RNAs category these lncRNA molecules operate as signals, decoys, guides, and scaffolds. In eukaryotes, lncRNAs are transcribed by RNA Polymerase II and RNA Polymerase III at several loci of the genome. Unlike other protein-coding mRNAs, lncRNAs exhibit functional uniqueness by participating in and modulating the various cellular processes such as, histone modification, DNA methylation, and cellular transcription (Wei et al., 2017). LncRNA alters chromatin structure and DNA accessibility, thereby regulating patterns of gene expression (Wang et al., 2011b). Disordered lncRNA with quantitative or qualitative alterations lead to the progression of numerous diseases including blood associated diseases. LncRNAs not only regulate lineage commitment such as cardiovascular lineage but also contribute for the hematopoietic stem cell development with a significant role in myeloid and lymphoid lineage commitment. However, the key molecular functions of lncRNAs in hematopoiesis are still unclear, particularly, their functional role during megakaryocyte development from hematopoietic stem cells (HSCs) is largely unexplored. This review summarizes the current status of knowledge on lncRNAs classification, biogenesis and its role in blood cells.
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                Author and article information

                Contributors
                bailin49@163.com
                qinchuan@pumc.edu.cn
                Journal
                Animal Model Exp Med
                Animal Model Exp Med
                10.1002/(ISSN)2576-2095
                AME2
                Animal Models and Experimental Medicine
                John Wiley and Sons Inc. (Hoboken )
                2096-5451
                2576-2095
                17 December 2019
                December 2019
                : 2
                : 4 ( doiID: 10.1002/ame2.v2.4 )
                : 239-251
                Affiliations
                [ 1 ] Institute of Medical Laboratory Animal Science Chinese Academy of Medical Sciences & Comparative Medical Center Peking Union Medical College Beijing China
                Author notes
                [*] [* ] Correspondence

                Chuan Qin and Lin Bai, Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing, China.

                Email: qinchuan@ 123456pumc.edu.cn (C.Q.); bailin49@ 123456163.com (L.B.)

                Author information
                https://orcid.org/0000-0003-1598-6581
                https://orcid.org/0000-0002-0646-0812
                Article
                AME212093
                10.1002/ame2.12093
                6930994
                31942556
                1777da1d-6886-4200-9465-f334098d165c
                © 2019 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 10 August 2019
                : 12 November 2019
                : 20 November 2019
                Page count
                Figures: 3, Tables: 2, Pages: 13, Words: 10090
                Funding
                Funded by: CAMS Innovation Fund for Medical Sciences
                Award ID: 2017‐I2M‐2‐005
                Award ID: 2016‐I2M‐2‐006
                Funded by: Beijing Natural Science Foundation , open-funder-registry 10.13039/501100005089;
                Award ID: 5171001
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                December 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:26.12.2019

                long noncoding rnas,neural development,neural differentiation,parkinson's disease,synapses

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