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      Role of long noncoding RNA in regulating HIV infection—a comprehensive review

      review-article
      1 , 1 ,
      mBio
      American Society for Microbiology
      human immunodeficiency virus, long noncoding RNA, HIV latency

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          ABSTRACT

          A complete cure against human immunodeficiency virus (HIV) infection remains out of reach, as the virus persists in stable cell reservoirs that are resistant to antiretroviral therapy. The key to eliminating these reservoirs lies in deciphering the processes that govern viral gene expression and latency. However, while we comprehensively understand how host proteins influence HIV gene expression and viral latency, the emerging role of long noncoding RNAs (lncRNAs) in the context of T cell activation, HIV gene expression, and viral latency remain unexplored. This review dives into the evolving significance of lncRNAs and their impact on HIV gene expression and viral latency. We provide an overview of the current knowledge regarding how lncRNAs regulate HIV gene expression, categorizing them as either activators or inhibitors of viral gene expression and infectivity. Furthermore, we offer insights into the potential therapeutic applications of lncRNAs in combatting HIV. A deeper understanding of how lncRNAs modulate HIV gene transcription holds promise for developing novel RNA-based therapies to complement existing treatment strategies to eradicate HIV reservoirs.

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          Most cited references168

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          Functional Classification and Experimental Dissection of Long Noncoding RNAs

          Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.
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            Unique features of long non-coding RNA biogenesis and function.

            Long non-coding RNAs (lncRNAs) are a diverse class of RNAs that engage in numerous biological processes across every branch of life. Although initially discovered as mRNA-like transcripts that do not encode proteins, recent studies have revealed features of lncRNAs that further distinguish them from mRNAs. In this Review, we describe special events in the lifetimes of lncRNAs - before, during and after transcription - and discuss how these events ultimately shape the unique characteristics and functional roles of lncRNAs.
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              Non-coding RNAs in human disease.

              The relevance of the non-coding genome to human disease has mainly been studied in the context of the widespread disruption of microRNA (miRNA) expression and function that is seen in human cancer. However, we are only beginning to understand the nature and extent of the involvement of non-coding RNAs (ncRNAs) in disease. Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis. Along with microRNAs, dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases. There is great interest in therapeutic strategies to counteract these perturbations of ncRNAs.
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                Author and article information

                Contributors
                Role: Writing – original draftRole: Writing – review and editing
                Role: Editor
                Journal
                mBio
                mBio
                mbio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                February 2024
                05 January 2024
                05 January 2024
                : 15
                : 2
                : e01925-23
                Affiliations
                [1 ]The Shraga Segal Department of Microbiology Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev; , Negev, Israel
                Albert Einstein College of Medicine; , Bronx, New York, USA
                Author notes
                Address correspondence to Ran Taube, rantaube@ 123456bgu.ac.il

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0009-0005-9570-985X
                https://orcid.org/0000-0002-2062-4537
                Article
                01925-23 mbio.01925-23
                10.1128/mbio.01925-23
                10865847
                38179937
                7e401926-c43b-4ab0-a6b9-bfc7ed5ef62a
                Copyright © 2024 Amir and Taube.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Page count
                supplementary-material: 0, authors: 2, Figures: 4, References: 169, Pages: 18, Words: 13455
                Funding
                Funded by: United States-Israel Bi-National Science Foundation (BSF);
                Award ID: 2021273
                Award Recipient :
                Funded by: Middle East DFG;
                Award ID: FA 378/13-2
                Award Recipient :
                Categories
                Minireview
                virology, Virology
                Custom metadata
                February 2024

                Life sciences
                human immunodeficiency virus,long noncoding rna,hiv latency
                Life sciences
                human immunodeficiency virus, long noncoding rna, hiv latency

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