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      Noncoding RNA therapeutics for substance use disorder

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          Abstract

          Although noncoding RNAs (ncRNAs) have been shown to regulate maladaptive neuroadaptations that drive compulsive drug use, ncRNA-targeting therapeutics for substance use disorder (SUD) have yet to be clinically tested. Recent advances in RNA-based drugs have improved many therapeutic issues related to immune response, specificity, and delivery, leading to multiple successful clinical trials for other diseases. As the need for safe and effective treatments for SUD continues to grow, novel nucleic acid-based therapeutics represent an appealing approach to target ncRNA mechanisms in SUD. Here, we review ncRNA processes implicated in SUD, discuss recent therapeutic approaches for targeting ncRNAs, and highlight potential opportunities and challenges of ncRNA-targeting therapeutics for SUD.

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          MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

          Rajesha Rupaimoole, Frank J Slack (2017)
          MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic.
          Article 0 comments Cited 1369 times – based on 0 reviews     Review now
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            Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

            Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)
            MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.
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              Regulation of microRNA biogenesis.

              Minju Ha, V Kim (2014)
              MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathological processes in animals. The biogenesis of miRNAs is under tight temporal and spatial control, and their dysregulation is associated with many human diseases, particularly cancer. In animals, miRNAs are ∼22 nucleotides in length, and they are produced by two RNase III proteins--Drosha and Dicer. miRNA biogenesis is regulated at multiple levels, including at the level of miRNA transcription; its processing by Drosha and Dicer in the nucleus and cytoplasm, respectively; its modification by RNA editing, RNA methylation, uridylation and adenylation; Argonaute loading; and RNA decay. Non-canonical pathways for miRNA biogenesis, including those that are independent of Drosha or Dicer, are also emerging.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9918335075006676
                Journal ID (pubmed-jr-id): 51357
                Journal ID (nlm-ta): Adv Drug Alcohol Res
                Journal ID (iso-abbrev): Adv Drug Alcohol Res
                Title: Advances in drug and alcohol research
                ISSN (Electronic): 2674-0001
                Publication date Nihms-submitted: 29 December 2022
                Publication date (Print): 2022
                Publication date (Electronic): 20 December 2022
                Publication date PMC-release: 03 January 2023
                Volume: 2
                Electronic Location Identifier: 10807
                Affiliations
                [1 ]Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, United States,
                [2 ]Connecticut Institute for the Brain and Cognitive Sciences (CT IBACS), Storrs, CT, United States
                Author notes

                Author contributions

                SAS wrote the manuscript with edits and feedback from GCS.

                [* ] CORRESPONDENCE: Gregory C. Sartor, Gregory.sartor@ 123456uconn.edu
                Article
                Manuscript ID: NIHMS1861278
                DOI: 10.3389/adar.2022.10807
                PMC ID: 9808746
                PubMed ID: 36601439
                SO-VID: f998af90-7eaa-479c-bb8d-2e321ab966f0
                License:

                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
                Categories
                Subject: Article

                Keywords: microrna,substance use disorder,noncoding rna,lncrna,smirna,circrna
                Data availability:
                Keywords: microrna, substance use disorder, noncoding rna, lncrna, smirna, circrna

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