miRNAs in Herpesvirus Infection: Powerful Regulators in Small Packages

microRNAs are a class of small, single-stranded, noncoding RNAs that regulate gene expression. They can be significantly dysregulated upon exposure to any infection, serving as important biomarkers and therapeutic targets. Numerous human DNA viruses, along with several herpesviruses, have been found to encode and express functional viral microRNAs known as vmiRNAs, which can play a vital role in host–pathogen interactions by controlling the viral life cycle and altering host biological pathways. Viruses have also adopted a variety of strategies to prevent being targeted by cellular miRNAs. Cellular miRNAs can act as anti- or proviral components, and their dysregulation occurs during a wide range of infections, including herpesvirus infection. This demonstrates the significance of miRNAs in host herpesvirus infection. The current state of knowledge regarding microRNAs and their role in the different stages of herpes virus infection are discussed in this review. It also delineates the therapeutic and biomarker potential of these microRNAs in future research directions.

[1]  Dongli Pan,et al.  Neuronal miR-138 Represses HSV-2 Lytic Infection by Regulating Viral and Host Genes with Mechanistic Differences from HSV-1 , 2022, Journal of virology.

[2]  S. Crooke,et al.  Antisense technology: an overview and prospectus , 2021, Nature Reviews Drug Discovery.

[3]  G. Church,et al.  Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus 1 latency , 2021, Nature Microbiology.

[4]  S. Kulkarni,et al.  Herpes Simplex Virus: The Hostile Guest That Takes Over Your Home , 2020, Frontiers in Microbiology.

[5]  Zhijun Liu,et al.  MicroRNAs expressed by human cytomegalovirus , 2020, Virology Journal.

[6]  R. Kamm,et al.  MicroRNA delivery through nanoparticles , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[7]  Ying Zhang,et al.  Herpes Simplex Virus Type 1–Encoded miR-H2-3p Manipulates Cytosolic DNA–Stimulated Antiviral Innate Immune Response by Targeting DDX41 , 2019, Viruses.

[8]  S. Badve,et al.  Predictive Biomarkers in Oncology , 2019, Springer International Publishing.

[9]  C. Taylor.  Introduction to Predictive Biomarkers: Definitions and Characteristics , 2018, Predictive Biomarkers in Oncology.

[10]  C. Peng,et al.  Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation , 2018, Front. Endocrinol..

[11]  D. Bloom,et al.  In Vivo Knockdown of the Herpes Simplex Virus 1 Latency-Associated Transcript Reduces Reactivation from Latency , 2018, Journal of Virology.

[12]  B. Rouse,et al.  Are miRNAs critical determinants in herpes simplex virus pathogenesis? , 2017, Microbes and infection.

[13]  G. Gao,et al.  Endogenous Cellular MicroRNAs Mediate Antiviral Defense against Influenza A Virus , 2017, Molecular therapy. Nucleic acids.

[14]  Yiting Xie,et al.  MicroRNA-373 facilitates HSV-1 replication through suppression of type I IFN response by targeting IRF1. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[15]  J. Connell,et al.  Plasma EBV microRNAs in paediatric renal transplant recipients , 2018, Journal of Nephrology.

[16]  H. Shroff,et al.  Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy , 2017, Nature Communications.

[17]  A. Nakano,et al.  MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus , 2017, Scientific Reports.

[18]  Yihui Deng,et al.  Differential expression of mRNA and miRNA in guinea pigs following infection with HSV2v , 2017, Experimental and therapeutic medicine.

[19]  H. Yoshiyama,et al.  Herpesviral microRNAs in Cellular Metabolism and Immune Responses , 2017, Front. Microbiol..

[20]  Li Zhou,et al.  MicroRNA‐649 promotes HSV‐1 replication by directly targeting MALT1 , 2017, Journal of medical virology.

[21]  Qiliang Cai,et al.  HCMV-encoded miR-UL112-3p promotes glioblastoma progression via tumour suppressor candidate 3 , 2017, Scientific Reports.

[22]  Xing-Xing He,et al.  MiR‐101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma , 2017, Cancer medicine.

[23]  Fei Yu,et al.  Self‐immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[24]  C. Cobbs,et al.  CMV70-3P miRNA contributes to the CMV mediated glioma stemness and represents a target for glioma experimental therapy , 2016, Oncotarget.

[25]  O. Mandelboim,et al.  HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion , 2016, Cell reports.

[26]  K. Riley,et al.  Epstein-Barr viral microRNAs target caspase 3 , 2016, Virology Journal.

[27]  J. M. Azevedo-Pereira,et al.  The Role of microRNAs in the Pathogenesis of Herpesvirus Infection , 2016, Viruses.

[28]  J. M. Azevedo-Pereira,et al.  MicroRNAs, HIV and HCV: a complex relation towards pathology , 2016, Reviews in medical virology.

[29]  Min Liu,et al.  ICP4-induced miR-101 attenuates HSV-1 replication , 2016, Scientific Reports.

[30]  B. Roizman,et al.  miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells , 2016, Proceedings of the National Academy of Sciences.

[31]  Suk-Kyeong Lee,et al.  Epstein-Barr Virus MicroRNA miR-BART20-5p Suppresses Lytic Induction by Inhibiting BAD-Mediated caspase-3-Dependent Apoptosis , 2015, Journal of Virology.

[32]  R. Jia,et al.  [Progress on the Function of Herpesvirus-encoded MicroRNAs]. , 2015, Bing du xue bao = Chinese journal of virology.

[33]  Alvaro G. Hernandez,et al.  Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers , 2015, PloS one.

[34]  B. Moerschbacher,et al.  Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells , 2015, Scientific Reports.

[35]  S. McWeeney,et al.  Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway , 2015, PLoS pathogens.

[36]  B. Rouse,et al.  Role of miR-155 in the pathogenesis of herpetic stromal keratitis. , 2015, The American journal of pathology.

[37]  Finn E. Grey,et al.  Role of microRNAs in herpesvirus latency and persistence. , 2015, The Journal of general virology.

[38]  Suk-Kyeong Lee,et al.  Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD. , 2015, Cancer letters.

[39]  Jennifer Louten,et al.  MicroRNAs Expressed during Viral Infection: Biomarker Potential and Therapeutic Considerations , 2015, Biomarker insights.

[40]  Min Liu,et al.  MiR-23a Facilitates the Replication of HSV-1 through the Suppression of Interferon Regulatory Factor 1 , 2014, PloS one.

[41]  F. Peruzzi,et al.  Role of Host MicroRNAs in Kaposi’s Sarcoma-Associated Herpesvirus Pathogenesis , 2014, Viruses.

[42]  H. Reyburn,et al.  Altered MicroRNA Expression after Infection with Human Cytomegalovirus Leads to TIMP3 Downregulation and Increased Shedding of Metalloprotease Substrates, Including MICA , 2014, The Journal of Immunology.

[43]  A. Abdelfattah,et al.  Update on non-canonical microRNAs , 2014, Biomolecular concepts.

[44]  B. Blencowe,et al.  Epstein-Barr Virus EBNA1 Protein Regulates Viral Latency through Effects on let-7 MicroRNA and Dicer , 2014, Journal of Virology.

[45]  B. Cullen,et al.  A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency. , 2014, Cell host & microbe.

[46]  T. Veiga-Parga,et al.  Critical Role of MicroRNA-155 in Herpes Simplex Encephalitis , 2014, The Journal of Immunology.

[47]  S. Rayner,et al.  MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a , 2014, Journal of Virology.

[48]  W. Britt,et al.  Cytomegalovirus microRNAs. , 2014, Current opinion in virology.

[49]  C. Lawrie.  MicroRNAs in Medicine , 2013 .

[50]  Pauline E. Chugh,et al.  Expression Profile of MicroRNAs in Epstein-Barr Virus-Infected AGS Gastric Carcinoma Cells , 2013, Journal of Virology.

[51]  H. Ørum.  Locked Nucleic Acids as MicroRNA Therapeutics , 2013 .

[52]  M. Joglekar,et al.  Circulating non-coding RNAs as biomarkers of beta cell death in diabetes. , 2013, Pediatric endocrinology reviews : PER.

[53]  S. Kojima,et al.  Plasma viral microRNA profiles reveal potential biomarkers for chronic active Epstein-Barr virus infection. , 2013, The Journal of infectious diseases.

[54]  Y. Qi,et al.  Over‐expression of human cytomegalovirus miR‐US25‐2‐3p downregulates eIF4A1 and inhibits HCMV replication , 2013, FEBS letters.

[55]  Honglin Chen,et al.  Targeting of DICE1 tumor suppressor by Epstein–Barr virus‐encoded miR‐BART3* microRNA in nasopharyngeal carcinoma , 2013, International journal of cancer.

[56]  Shou-Jiang Gao,et al.  γ-Herpesvirus-encoded miRNAs and their roles in viral biology and pathogenesis. , 2013, Current opinion in virology.

[57]  Xuemei Zhang,et al.  A microRNA encoded by HSV-1 inhibits a cellular transcriptional repressor of viral immediate early and early genes , 2013, Science China Life Sciences.

[58]  C. Kotton.  CMV: Prevention, Diagnosis and Therapy , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[59]  Katie Podshivalova,et al.  MicroRNA regulation of T-lymphocyte immunity: modulation of molecular networks responsible for T-cell activation, differentiation, and development. , 2013, Critical reviews in immunology.

[60]  L. BenMohamed,et al.  Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections , 2012, Clinical & developmental immunology.

[61]  Qihan Li,et al.  The miRNAs of Herpes Simplex Virus (HSV) , 2012, Virologica Sinica.

[62]  W. Hammerschmidt,et al.  This information is current as Production β Inflammasome and IL-1 miR-BART 15 Regulate the NLRP 3 Cutting Edge : miR-223 and EBV , 2012 .

[63]  L. BenMohamed,et al.  Targeting the Genital Tract Mucosa with a Lipopeptide/Recombinant Adenovirus Prime/Boost Vaccine Induces Potent and Long-Lasting CD8+ T Cell Immunity against Herpes: Importance of MyD88 , 2012, The Journal of Immunology.

[64]  Yufei Huang,et al.  A Kaposi's Sarcoma-Associated Herpesvirus MicroRNA and Its Variants Target the Transforming Growth Factor β Pathway To Promote Cell Survival , 2012, Journal of Virology.

[65]  J. Ziegelbauer,et al.  Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs Target IRAK1 and MYD88, Two Components of the Toll-Like Receptor/Interleukin-1R Signaling Cascade, To Reduce Inflammatory-Cytokine Expression , 2012, Journal of Virology.

[66]  G. Meister,et al.  MicroRNA Profiling of Epstein-Barr Virus-Associated NK/T-Cell Lymphomas by Deep Sequencing , 2012, PloS one.

[67]  Shalini Sharma,et al.  Role of miR-132 in angiogenesis after ocular infection with herpes simplex virus. , 2012, The American journal of pathology.

[68]  W. Hammerschmidt,et al.  The EBV Immunoevasins vIL-10 and BNLF2a Protect Newly Infected B Cells from Immune Recognition and Elimination , 2012, PLoS pathogens.

[69]  Kaili Wu,et al.  HSV-1 miR-H6 Inhibits HSV-1 Replication and IL-6 Expression in Human Corneal Epithelial Cells In Vitro , 2012, Clinical & developmental immunology.

[70]  A. Nesburn,et al.  Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: The Old, the New, and the Unknown , 2012, Clinical & developmental immunology.

[71]  Jin-Hyun Ahn,et al.  Human Cytomegalovirus Clinical Strain-Specific microRNA miR-UL148D Targets the Human Chemokine RANTES during Infection , 2012, PLoS pathogens.

[72]  Z. Qin,et al.  KSHV-Encoded MicroRNAs: Lessons for Viral Cancer Pathogenesis and Emerging Concepts , 2012, International journal of cell biology.

[73]  D. Kwong,et al.  Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs , 2012, Cancer.

[74]  V. Beneš,et al.  Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis , 2011, PLoS pathogens.

[75]  R. Renne,et al.  Viral miRNAs and immune evasion. , 2011, Biochimica et biophysica acta.

[76]  G. Meister,et al.  EBV-encoded miRNAs. , 2011, Biochimica et biophysica acta.

[77]  Xianzhi Lin,et al.  Kaposi's Sarcoma-Associated Herpesvirus-Encoded MicroRNA miR-K12-11 Attenuates Transforming Growth Factor Beta Signaling through Suppression of SMAD5 , 2011, Journal of Virology.

[78]  D. Powell,et al.  Oral acyclovir suppression and neurodevelopment after neonatal herpes. , 2011, The New England journal of medicine.

[79]  S. Riddell,et al.  Human cytomegalovirus microRNA miR-US4-1 inhibits CD8+ T cell responses by targeting the aminopeptidase ERAP1 , 2011, Nature Immunology.

[80]  B. Cullen.  Herpesvirus microRNAs: phenotypes and functions. , 2011, Current opinion in virology.

[81]  O. Mandelboim,et al.  MicroRNA based immunoevasion mechanism of human polyomaviruses , 2011, RNA biology.

[82]  Qiang Deng,et al.  A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKK ε , 2011 .

[83]  N. Raab-Traub,et al.  The Epstein-Barr Virus BART microRNAs target the pro-apoptotic protein Bim. , 2011, Virology.

[84]  Yan Zhang,et al.  MiR-101 regulates HSV-1 replication by targeting ATP5B. , 2011, Antiviral research.

[85]  T. Margolis,et al.  Herpes Simplex Virus 2 MicroRNA miR-H6 Is a Novel Latency-Associated Transcript-Associated MicroRNA, but Reduction of Its Expression Does Not Influence the Establishment of Viral Latency or the Recurrence Phenotype , 2011, Journal of Virology.

[86]  E. Robertson,et al.  miR-K12-7-5p Encoded by Kaposi's Sarcoma-Associated Herpesvirus Stabilizes the Latent State by Targeting Viral ORF50/RTA , 2011, PloS one.

[87]  Ana Kozomara,et al.  miRBase: integrating microRNA annotation and deep-sequencing data , 2010, Nucleic Acids Res..

[88]  N. Raab-Traub,et al.  Human tumor virus utilizes exosomes for intercellular communication , 2010, Proceedings of the National Academy of Sciences.

[89]  Dieter Jocham,et al.  A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. , 2010, Urologic oncology.

[90]  Zhonghan Li,et al.  MicroRNAs encoded by Kaposi's sarcoma‐associated herpesvirus regulate viral life cycle , 2010, EMBO reports.

[91]  J. Ziegelbauer,et al.  Regulation of Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Receptor Protein (TWEAKR) Expression by Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Prevents TWEAK-Induced Apoptosis and Inflammatory Cytokine Expression , 2010, Journal of Virology.

[92]  Xiu-fen Lei,et al.  Regulation of herpes virus lifecycle by viral microRNAs , 2010, Virulence.

[93]  A. Hatzigeorgiou,et al.  Editing of Epstein-Barr Virus-encoded BART6 MicroRNAs Controls Their Dicer Targeting and Consequently Affects Viral Latency* , 2010, The Journal of Biological Chemistry.

[94]  J. Mertz,et al.  Cellular MicroRNAs 200b and 429 Regulate the Epstein-Barr Virus Switch between Latency and Lytic Replication , 2010, Journal of Virology.

[95]  Anton J. Enright,et al.  Combined agonist–antagonist genome-wide functional screening identifies broadly active antiviral microRNAs , 2010, Proceedings of the National Academy of Sciences.

[96]  Frances Gotch,et al.  miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator , 2010, Nature Cell Biology.

[97]  B. Cullen,et al.  A Human Herpesvirus MicroRNA Inhibits p21 Expression and Attenuates p21-Mediated Cell Cycle Arrest , 2010, Journal of Virology.

[98]  J. Mellor,et al.  Numerous Conserved and Divergent MicroRNAs Expressed by Herpes Simplex Viruses 1 and 2 , 2010, Journal of Virology.

[99]  Paul Kellam,et al.  KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. , 2010, Genes & development.

[100]  William Stedman,et al.  Epigenetic Regulation of Kaposi's Sarcoma-Associated Herpesvirus Latency by Virus-Encoded MicroRNAs That Target Rta and the Cellular Rbl2-DNMT Pathway , 2010, Journal of Virology.

[101]  S. Kauppinen,et al.  Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection , 2010, Science.

[102]  Z. Qin,et al.  Upregulation of xCT by KSHV-Encoded microRNAs Facilitates KSHV Dissemination and Persistence in an Environment of Oxidative Stress , 2010, PLoS pathogens.

[103]  Yufei Huang,et al.  Regulation of NF-κB inhibitor IκBα and viral replication by a KSHV microRNA , 2009, Nature Cell Biology.

[104]  R. Renne,et al.  Role of virus-encoded microRNAs in herpesvirus biology. , 2009, Trends in microbiology.

[105]  B. Cullen,et al.  Identification of Viral MicroRNAs Expressed in Human Sacral Ganglia Latently Infected with Herpes Simplex Virus 2 , 2009, Journal of Virology.

[106]  Raymond Wai-Ming Lung,et al.  Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22. , 2009, Neoplasia.

[107]  N. Park,et al.  Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection , 2009, Clinical Cancer Research.

[108]  Noam Stern-Ginossar,et al.  Analysis of Human Cytomegalovirus-Encoded MicroRNA Activity during Infection , 2009, Journal of Virology.

[109]  W. Filipowicz,et al.  Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. , 2009, Current opinion in cell biology.

[110]  Noam Stern-Ginossar,et al.  Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. , 2009, Cell host & microbe.

[111]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[112]  D. Ganem,et al.  Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs , 2009, Nature Genetics.

[113]  P. Krause,et al.  Novel Less-Abundant Viral MicroRNAs Encoded by Herpes Simplex Virus 2 Latency-Associated Transcript and Their Roles in Regulating ICP34.5 and ICP0 mRNAs , 2008, Journal of Virology.

[114]  Shing-Jyh Chang,et al.  The M Type K15 Protein of Kaposi's Sarcoma-Associated Herpesvirus Regulates MicroRNA Expression via Its SH2-Binding Motif To Induce Cell Migration and Invasion , 2008, Journal of Virology.

[115]  D. Kwong,et al.  An Epstein-Barr virus–encoded microRNA targets PUMA to promote host cell survival , 2008, The Journal of experimental medicine.

[116]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[117]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[118]  J. Cohen,et al.  An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor , 2008, Proceedings of the National Academy of Sciences.

[119]  B. Cullen,et al.  MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs , 2008, Nature.

[120]  A. Harris,et al.  Detection of elevated levels of tumour‐associated microRNAs in serum of patients with diffuse large B‐cell lymphoma , 2008, British journal of haematology.

[121]  Jirí Vanícek,et al.  Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: Implications for latency , 2008, Proceedings of the National Academy of Sciences.

[122]  Andrea J. O'Hara,et al.  EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. , 2008, Cancer research.

[123]  K. Roemer,et al.  Epstein–Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5 , 2007, Nucleic acids research.

[124]  Jay Nelson,et al.  The functions of herpesvirus-encoded microRNAs , 2008, Medical Microbiology and Immunology.

[125]  Bryan R. Cullen,et al.  A viral microRNA functions as an orthologue of cellular miR-155 , 2007, Nature.

[126]  Kwok Wai Lo,et al.  Modulation of LMP1 protein expression by EBV-encoded microRNAs , 2007, Proceedings of the National Academy of Sciences.

[127]  Alberto Riva,et al.  Kaposi's Sarcoma-Associated Herpesvirus Encodes an Ortholog of miR-155 , 2007, Journal of Virology.

[128]  Hanah Margalit,et al.  Host Immune System Gene Targeting by a Viral miRNA , 2007, Science.

[129]  B. O'Sullivan,et al.  Epstein–Barr virus-associated tumours: an update for the attention of the working pathologist , 2006, Journal of Clinical Pathology.

[130]  Guanglin Li,et al.  Prediction and Identification of Herpes Simplex Virus 1-Encoded MicroRNAs , 2006, Journal of Virology.

[131]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[132]  B. Rouse,et al.  Early events in HSV keratitis--setting the stage for a blinding disease. , 2005, Microbes and infection.

[133]  C. Sander,et al.  Identification of microRNAs of the herpesvirus family , 2005, Nature Methods.

[134]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

[135]  G. Hannon,et al.  Processing of primary microRNAs by the Microprocessor complex , 2004, Nature.

[136]  Karlie Plaisance-Bonstaff,et al.  Viral miRNAs , 2004, Science's STKE.

[137]  Anton J. Enright,et al.  Identification of Virus-Encoded MicroRNAs , 2004, Science.

[138]  John G Doench,et al.  Specificity of microRNA target selection in translational repression. , 2004, Genes & development.

[139]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[140]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[141]  A. Pasquinelli,et al.  A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA , 2001, Science.

[142]  R. Everett.  ICP0, a regulator of herpes simplex virus during lytic and latent infection. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[143]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[144]  S. Deshmane,et al.  During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure , 1989, Journal of virology.