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      Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior

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          Abstract

          It is well known that only a small proportion of the human genome code for proteins; the rest belong to the family of RNAs that do not code for protein and are known as non-coding RNAs (ncRNAs). ncRNAs are further divided into two subclasses based on size: 1) long non-coding RNAs (lncRNAs; >200 nucleotides) and 2) small RNAs (<200 nucleotides). Small RNAs contain various family members that include microRNAs (miRNAs), small interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and small nuclear RNAs (snRNAs). The roles of ncRNAs, especially lncRNAs and miRNAs, are well documented in brain development, homeostasis, stress responses, and neural plasticity. It has also been reported that ncRNAs can influence the development of psychiatric disorders including schizophrenia, major depressive disorder, and bipolar disorder. More recently, their roles are being investigated in suicidal behavior. In this article, we have comprehensively reviewed the findings of lncRNA and miRNA expression changes and their functions in various psychiatric disorders including suicidal behavior. We primarily focused on studies that have been done in postmortem human brain. In addition, we have briefly reviewed the role of other small RNAs ( e.g. piwiRNA, siRNA, snRNA, and snoRNAs) and their expression changes in psychiatric illnesses.

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          Most cited references196

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          An Integrated Encyclopedia of DNA Elements in the Human Genome

          Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research.
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            Biological Insights From 108 Schizophrenia-Associated Genetic Loci

            Summary Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia.
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              The transcriptional landscape of the mammalian genome.

              This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                15 September 2020
                2020
                : 11
                : 543893
                Affiliations
                [1] Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham , Birmingham, AL, United States
                Author notes

                Edited by: Maurizio Pompili, Sapienza University of Rome, Italy

                Reviewed by: Miao Qu, Xuanwu Hospital, Capital Medical University, China; Peter Petschner, Semmelweis University, Hungary

                *Correspondence: Yogesh Dwivedi, yogeshdwivedi@ 123456uabmc.edu

                This article was submitted to Mood and Anxiety Disorders, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2020.543893
                7522197
                33101077
                5201ba93-f62a-4230-a053-42053341794d
                Copyright © 2020 Yoshino and Dwivedi

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 March 2020
                : 14 August 2020
                Page count
                Figures: 3, Tables: 5, Equations: 0, References: 196, Pages: 20, Words: 9247
                Funding
                Funded by: National Institute of Mental Health 10.13039/100000025
                Funded by: National Institute of Mental Health 10.13039/100000025
                Funded by: National Institute of Mental Health 10.13039/100000025
                Funded by: National Institute for Medical Research Development 10.13039/501100012155
                Funded by: National Institute of Mental Health 10.13039/100000025
                Categories
                Psychiatry
                Review

                Clinical Psychology & Psychiatry
                major depressive disorder,schizophrenia,bipolar disorder,long non-coding rnas,micrornas

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