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      Is Open Access

      Regulation of Latency and Reactivation by Human Cytomegalovirus miRNAs

      review-article
      , , *
      Pathogens
      MDPI
      cytomegalovirus, miRNA, latency, signaling

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          Abstract

          Human cytomegalovirus (HCMV) encodes 22 mature microRNAs (miRNAs), which regulate a myriad of cellular processes, including vesicular trafficking, cell cycle progression, apoptosis, and immune evasion, as well as viral gene expression. Recent evidence points to a critical role for HCMV miRNAs in mediating latency in CD34 + hematopoietic progenitor cells through modulation of cellular signaling pathways, including attenuation of TGFβ and EGFR signaling. Moreover, HCMV miRNAs can act in concert with, or in opposition to, viral proteins in regulating host cell functions. Here, we comprehensively review the studies of HCMV miRNAs in the context of latency and highlight the novel processes that are manipulated by the virus using these small non-coding RNAs.

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          Most cited references107

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          MicroRNAs: target recognition and regulatory functions.

          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            Metazoan MicroRNAs

            MicroRNAs (miRNAs) are ∼22 nt RNAs that direct posttranscriptional repression of mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these small RNAs help sculpt the expression of most mRNAs. This article reviews advances in our understanding of the defining features of metazoan miRNAs and their biogenesis, genomics, and evolution. It then reviews how metazoan miRNAs are regulated, how they recognize and cause repression of their targets, and the biological functions of this repression, with a compilation of knockout phenotypes that shows that important biological functions have been identified for most of the broadly conserved miRNAs of mammals.
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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

                Contributors
                Role: Academic Editor
                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                13 February 2021
                February 2021
                : 10
                : 2
                : 200
                Affiliations
                Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA; diggins@ 123456ohsu.edu (N.L.D.); skalsky@ 123456ohsu.edu (R.L.S.)
                Author notes
                [* ]Correspondence: hancocme@ 123456ohsu.edu ; Tel.: +1-503-418-2756
                Author information
                https://orcid.org/0000-0003-2945-0147
                Article
                pathogens-10-00200
                10.3390/pathogens10020200
                7918750
                33668486
                a6d42943-9773-4678-b0e2-7402488b745a
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 January 2021
                : 10 February 2021
                Categories
                Review

                cytomegalovirus,mirna,latency,signaling
                cytomegalovirus, mirna, latency, signaling

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