MicroRNAs; Animals; Carps; Fish Diseases/virology; Herpesviridae/genetics; Herpesviridae/pathogenicity; Herpesviridae Infections/virology; MicroRNAs/genetics; Fish Diseases; Herpesviridae; Herpesviridae Infections; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); Multidisciplinary
Abstract :
[en] MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in post-transcriptional gene regulation. Some viruses encode their own miRNAs and these are increasingly being recognized as important modulators of viral and host gene expression. Cyprinid herpesvirus 3 (CyHV-3) is a highly pathogenic agent that causes acute mass mortalities in carp (Cyprinus carpio carpio) and koi (Cyprinus carpio koi) worldwide. Here, bioinformatic analyses of the CyHV-3 genome suggested the presence of non-conserved precursor miRNA (pre-miRNA) genes. Deep sequencing of small RNA fractions prepared from in vitro CyHV-3 infections led to the identification of potential miRNAs and miRNA-offset RNAs (moRNAs) derived from some bioinformatically predicted pre-miRNAs. DNA microarray hybridization analysis, Northern blotting and stem-loop RT-qPCR were then used to definitively confirm that CyHV-3 expresses two pre-miRNAs during infection in vitro. The evidence also suggested the presence of an additional four high-probability and two putative viral pre-miRNAs. MiRNAs from the two confirmed pre-miRNAs were also detected in gill tissue from CyHV-3-infected carp. We also present evidence that one confirmed miRNA can regulate the expression of a putative CyHV-3-encoded dUTPase. Candidate homologues of some CyHV-3 pre-miRNAs were identified in CyHV-1 and CyHV-2. This is the first report of miRNA and moRNA genes encoded by members of the Alloherpesviridae family, a group distantly related to the Herpesviridae family. The discovery of these novel CyHV-3 genes may help further our understanding of the biology of this economically important virus and their encoded miRNAs may have potential as biomarkers for the diagnosis of latent CyHV-3.
Disciplines :
Genetics & genetic processes
Author, co-author :
Donohoe, Owen ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire ; Marine Institute, Rinville, Oranmore, Co. Galway, Ireland, School of Biotechnology and National Centre for Sensor Research, Dublin City University, Dublin, Ireland
Henshilwood, Kathy; Marine Institute, Rinville, Oranmore, Co. Galway, Ireland
Way, Keith; Centre for Environment, Fisheries and Aquaculture Science (Cefas), The Nothe, Weymouth, Dorset, the United Kingdom
Hakimjavadi, Roya; School of Biotechnology and National Centre for Sensor Research, Dublin City University, Dublin, Ireland
Stone, David M; Centre for Environment, Fisheries and Aquaculture Science (Cefas), The Nothe, Weymouth, Dorset, the United Kingdom
Walls, Dermot; School of Biotechnology and National Centre for Sensor Research, Dublin City University, Dublin, Ireland
Language :
English
Title :
Identification and Characterization of Cyprinid Herpesvirus-3 (CyHV-3) Encoded MicroRNAs.
This work was supported by the Marine Institute Research Fellowship programme (https:// www.marine.ie; OHD), Defra (https://www.gov.uk/ government/organisations/department-forenvironment- food-rural-affairs; research contracts FC1193 and FC1202; KW), the Programme for Research in Third Level Institutions (PRTLI) (http:// www.hea.ie/en/prtli,official; RH, DW) Cycle 5 [The Bioanalysis and Therapeutics (BioAT) programme at DCU]. The PRTLI is co-funded through the European Regional Development Fund (ERDF), part of the European Union Structural Funds Programme 2007- 2013 (http://eustructuralfunds.gov.ie). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are grateful to Dr. Stephen McCleary, Dr. Neil Ruane, David Swords, Lorraine McCarthy and Dr. Margret Rae (Marine Institute, Galway, Ireland), Laura Naughton and Sarah Faherty O''Donnell (Dublin City University), Dr. Elaine Kennedy (TrinSeq Core Facility, Dublin, Ireland) and Dr. Donald Schwartz (MYcorarray, Ann Arbor, MI, USA) for their kind assistance at various stages of this study.
Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107:823-826. PMID: 11779458
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853-858. PMID: 11679670
Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001;294:858-862. PMID: 11679671
Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001;294:862-864. PMID: 11679672
Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126-139. doi: 10.1038/nrm2632 PMID: 19165215
Nozawa M, Miura S, Nei M. Origins and Evolution of MicroRNA Genes in Drosophila Species. Genome Biol Evol. 2010;2:180-189. doi: 10.1093/gbe/evq009 PMID: 20624724
Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14:1902-1910. PMID: 15364901
Han J, Lee Y, Yeom K-H, Nam J-W, Heo I, Rhee J-K, et al. Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 Complex. Cell. 2006;125:887-901. PMID: 16751099
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415-419. PMID: 14508493
Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740-744. PMID: 15973356
Ji X. The mechanism of RNase III action: how dicer dices. Curr Top Microbiol Immunol. 2008;320:99-116. PMID: 18268841
Koscianska E, Starega-Roslan J, Krzyzosiak WJ. The Role of Dicer Protein Partners in the Processing of MicroRNA Precursors. PLoS One. 2011;6:e28548. doi: 10.1371/journal.pone.0028548 PMID: 22163034
Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs Exhibit Strand Bias. Cell. 2003;115:209-216. PMID: 14567918
Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the Assembly of the RNAi Enzyme Complex. Cell. 2003;115:199-208. PMID: 14567917
FilipowiczW, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by micro-RNAs: are the answers in sight? Nat Rev Genet. 2008;9:102-114. doi: 10.1038/nrg2290 PMID: 18197166
Gu S, Kay MA. How do miRNAs mediate translational repression? Silence. 2010;1:11. doi: 10.1186/1758-907X-1-11 PMID: 20459656
Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 2011;12:99-110. doi: 10.1038/nrg2936 PMID: 21245828
Su H, Trombly MI, Chen J, Wang X. Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes Dev. 2009;23:304-317. doi: 10.1101/gad.1749809 PMID: 19174539
Morin RD, O'Connor MD, Griffith M, Kuchenbauer F, Delaney A, Prabhu A-L, et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res. 2008;18:610-621. doi: 10.1101/gr.7179508 PMID: 18285502
Bortoluzzi S, Biasiolo M, Bisognin A. Micro RNA-offset RNAs (moRNAs): by-product spectators or functional players? TrendsMol Med. 2011;17:473-474. doi: 10.1016/j.molmed.2011.05.005 PMID: 21700497
Langenberger D, Bermudez-Santana C, Hertel J, Hoffmann S, Khaitovich P, Stadler PF. Evidence for human microRNA-offset RNAs in small RNA sequencing data. Bioinformatics. 2009;25:2298-2301. doi: 10.1093/bioinformatics/btp419 PMID: 19584066
Shi W, Hendrix D, Levine M, Haley B. A distinct class of small RNAs arises from pre-miRNA-proximal regions in a simple chordate. Nat Struct Mol Biol. 2009;16:183-189. doi: 10.1038/nsmb.1536 PMID: 19151725
Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science. 2004;304:734-736. PMID: 15118162
Kincaid RP, Sullivan CS. Virus-Encoded microRNAs: An Overview and a Look to the Future. PLoS Pathog. 2012;8:e1003018. doi: 10.1371/journal.ppat.1003018 PMID: 23308061
Skalsky RL, Cullen BR. Viruses, microRNAs, and Host Interactions. Annu Rev Microbiol. 2010;64:123-141. doi: 10.1146/annurev. micro.112408.134243 PMID: 20477536
Cullen BR. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev. 2011;25:1881-1894. doi: 10.1101/gad.17352611 PMID: 21896651
Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, et al. Identification of microRNAs of the herpesvirus family. Nat Methods. 2005;2:269-276. PMID: 15782219
Hanson L, Dishon A, Kotler M. Herpesviruses that Infect Fish. Viruses. 2011;3:2160-2191. doi: 10. 3390/v3112160 PMID: 22163339
Davison AJ. Evolution of the herpesviruses. Vet Microbiol. 2002;86:69-88. PMID: 11888691
Davison AJ, Eberle R, Ehlers B, Hayward GS, McGeoch DJ, Minson AC, et al. The order Herpesvirales. Arch Virol. 2009;154:171-177. doi: 10.1007/s00705-008-0278-4 PMID: 19066710
Waltzek TB, Kelley GO, Alfaro ME, Kurobe T, Davison AJ, Hedrick RP. Phylogenetic relationships in the family Alloherpesviridae. Dis Aquat Organ. 2009;84:179-194. doi: 10.3354/dao02023 PMID: 19565695
Ilouze M, Davidovich M, Diamant A, Kotler M, Dishon A. The outbreak of carp disease caused by CyHV-3 as a model for new emerging viral diseases in aquaculture: a review. Ecol Res. 2011;26:885-892.
Pokorova D, Vesely T, Piackova V. Current Knowledge on koi Herpesvirus-A review. Vet Med (Praha). 2005;50:139-147.
Gotesman M, Kattlun J, Bergmann SM, El-Matbouli M. CyHV-3: the third cyprinid herpesvirus. Dis Aquat Organ. 2013;105:163-174. doi: 10.3354/dao02614 PMID: 23872859
Rakus K, Ouyang P, Boutier M, Ronsmans M, Reschner A, Vancsok C, et al. Cyprinid herpesvirus 3: an interesting virus for applied and fundamental research. Vet Res. 2013;44:85. doi: 10.1186/1297-9716-44-85 PMID: 24073814
Haenen OLM, Way K, Bergmann SM, Ariel E. The emergence of koi herpesvirus and its significance to European aquaculture. Bull Eur Assoc Fish Pathol. 2004;24:293-307.
Hedrick RP, Gilad O, Yun S, Spangenberg JV, Marty GD, Nordhausen RW, et al. A Herpesvirus Associated with Mass Mortality of Juvenile and Adult Koi, a Strain of Common Carp. J Aquat Anim Health. 2000;12:44-57.
Ilouze M, Dishon A, Kotler M. Characterization of a novel virus causing a lethal disease in carp and koi. Microbiol Mol Biol Rev. 2006;70:147-156. PMID: 16524920
Perelberg A, Smirnov M, Hutoran M, Diamant A, Bejerano Y, Kotler M. Epidemiological description of a new viral disease afflicting cultured Cyprinus carpio in Israel. Isr J Aquacult-Bamid. 2003;55:5-12.
Pearson H. Carp virus crisis prompts moves to avert global spread. Nature. 2004;427:577. PMID: 14961088
Liao IC, Chao N-H. Aquaculture and food crisis: opportunities and constraints. Asia Pac J Clin Nutr. 2009;18:564-569. PMID: 19965349
Eide KE, Miller-Morgan T, Heidel JR, Kent ML, Bildfell RJ, Lapatra S, et al. Investigation of koi herpesvirus latency in koi. J Virol. 2011;85:4954-4962. doi: 10.1128/JVI.01384-10 PMID: 21389134
Gilad O, Yun S, Zagmutt-Vergara FJ, Leutenegger CM, Bercovier H, Hedrick RP. Concentrations of a Koi herpesvirus (KHV) in tissues of experimentally infected Cyprinus carpio koi as assessed by realtime TaqMan PCR. Dis Aquat Organ. 2004;60:179-187. PMID: 15521316
Reed AN, Izume S, Dolan BP, La Patra S, Kent M, Dong J, et al. Identification of B cells as a major site for cyprinid herpesvirus 3 latency. J Virol. 2014;88:9297-9309. doi: 10.1128/JVI.00990-14 PMID: 24899202
Xu J-R, Bently J, Beck L, Reed A, Miller-Morgan T, Heidel JR, et al. Analysis of koi herpesvirus latency in wild common carp and ornamental koi in Oregon, USA. J Virol Methods. 2013;187:372-379. doi: 10.1016/j.jviromet.2012.11.015 PMID: 23174162
St-Hilaire S, Beevers N, Way K, Le Deuff RM, Martin P, Joiner C. Reactivation of koi herpesvirus infections in common carp Cyprinus carpio. Dis Aquat Organ. 2005;67:15-23. PMID: 16385803
Grundhoff A, Sullivan CS, Ganem D. A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. RNA. 2006;12:733-750. PMID: 16540699
Neukirch M, Böttcher K, Bunnajirakul S. Isolation of a virus from koi with altered gills. Bull Eur Assoc Fish Pathol. 1999;19:221-224.
Engelsma MY, Way K, Dodge MJ, Voorbergen-Laarman M, Panzarin V, Abbadi M, et al. Detection of novel strains of cyprinid herpesvirus closely related to koi herpesvirus. Dis Aquat Organ. 2013;107:113-120. doi: 10.3354/dao02666 PMID: 24334353
Sullivan CS, Grundhoff A. Identification of viral microRNAs. Meth Enzymol. 2007;427:3-23. PMID: 17720476
Jiang H, Wong WH. SeqMap: mapping massive amount of oligonucleotides to the genome. Bioinformatics. 2008;24:2395-2396. doi: 10.1093/bioinformatics/btn429 PMID: 18697769
Jiang P, Wu H, Wang W, Ma W, Sun X, Lu Z. MiPred: classification of real and pseudo microRNA precursors using random forest prediction model with combined features. Nucleic Acids Res. 2007;35:W339-W344. PMID: 17553836
Agarwal S, Vaz C, Bhattacharya A, Srinivasan A. Prediction of novel precursor miRNAs using a contextsensitive hidden Markov model (CSHMM). BMC Bioinformatics. 2010;11:S29. doi: 10.1186/1471-2105-11-S6-S29 PMID: 20946613
Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39:D152-157. doi: 10.1093/nar/gkq1027 PMID: 21037258
Friedländer MR, Mackowiak SD, Li N, Chen W, Rajewsky N. miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res. 2012;40:37-52. doi: 10.1093/nar/gkr688 PMID: 21911355
Friedländer MR, Chen W, Adamidi C, Maaskola J, Einspanier R, Knespel S, et al. Discovering micro-RNAs from deep sequencing data using miRDeep. Nat Biotechnol. 2008;26:407-415. doi: 10.1038/nbt1394 PMID: 18392026
sourceforge.net. MicroRNA Discovery By Deep Sequencing [Internet]. 4 Oct. 2013. Available: http://sourceforge.net/projects/mireap/. Accessed 2013 Apr. 1.
Barad O, Meiri E, Avniel A, Aharonov R, Barzilai A, Bentwich I, et al. MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res. 2004;14:2486-2494. PMID: 15574827
Ruijter JM, Ramakers C, Hoogaars WMH, Karlen Y, Bakker O, van den Hoff MJB, et al. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009;37:e45. doi: 10.1093/nar/gkp045 PMID: 19237396
Takane K, Kanai A. Vertebrate virus-encoded microRNAs and their sequence conservation. Jpn J Infect Dis. 2011;64:357-366. PMID: 21937815
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15-20. PMID: 15652477
Garcia DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP. Weak seed-pairing stability and high targetsite abundance decrease the proficiency of lsy-6 and other microRNAs. Nat Struct Mol Biol. 2011;18:1139-1146. doi: 10.1038/nsmb.2115 PMID: 21909094
Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E. The role of site accessibility in microRNA target recognition. Nat Genet. 2007;39:1278-1284. PMID: 17893677
Welch BL. The Generalization of 'Student's' Problem when Several Different Population Variances are Involved. Biometrika. 1947;34:28. PMID: 20287819
Campion EM, Hakimjavadi R, Loughran ST, Phelan S, Smith SM, D'Souza BN, et al. Repression of the pro-apoptotic cellular BIK/NBK gene by Epstein-Barr virus antagonises TGF-β1-induced B-cell apoptosis. J Virol. 2014; JVI.03642-13. doi: 10.1128/JVI.03642-13 PMID: 24554662
Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, Cullen BR. Analysis of Human Alphaherpesvirus Micro-RNA Expression in Latently Infected Human Trigeminal Ganglia. J Virol. 2009;83:10677-10683. doi: 10.1128/JVI.01185-09 PMID: 19656888
Bonnet E, Wuyts J, Rouzé P, Van de Peer Y. Evidence that microRNA precursors, unlike other noncoding RNAs, have lower folding free energies than random sequences. Bioinformatics. 2004;20:2911-2917. PMID: 15217813
Berezikov E, Robine N, Samsonova A, Westholm JO, Naqvi A, Hung J-H, et al. Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence. Genome Res. 2011;21:203-215. doi: 10.1101/gr.116657.110 PMID: 21177969
Bortoluzzi S, Bisognin A, Biasiolo M, Guglielmelli P, Biamonte F, Norfo R, et al. Characterization and discovery of novel miRNAs and moRNAs in JAK2V617F-mutated SET2 cells. Blood. 2012;119:e120-130. doi: 10.1182/blood-2011-07-368001 PMID: 22223824
Lee LW, Zhang S, Etheridge A, Ma L, Martin D, Galas D, et al. Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA. 2010;16:2170-2180. doi: 10.1261/rna.2225110 PMID: 20876832
Ruby JG, Stark A, Johnston WK, Kellis M, Bartel DP, Lai EC. Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs. Genome Res. 2007;17:1850-1864. PMID: 17989254
Berezikov E. Evolution of microRNA diversity and regulation in animals. Nat Rev Genet. 2011;12:846-860. doi: 10.1038/nrg3079 PMID: 22094948
Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of micro-RNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33:e179. PMID: 16314309
Davison AJ, Kurobe T, Gatherer D, Cunningham C, Korf I, Fukuda H, et al. Comparative genomics of carp herpesviruses. J Virol. 2013;87:2908-2922. doi: 10.1128/JVI.03206-12 PMID: 23269803
Waltzek TB, Kelley GO, Stone DM, Way K, Hanson L, Fukuda H, et al. Koi herpesvirus represents a third cyprinid herpesvirus (CyHV-3) in the family Herpesviridae. J Gen Virol. 2005;86:1659-67. PMID: 15914843
Aoki T, Hirono I, Kurokawa K, Fukuda H, Nahary R, Eldar A, et al. Genome sequences of three koi herpesvirus isolates representing the expanding distribution of an emerging disease threatening koi and common carp worldwide. J Virol. 2007;81:5058-65. PMID: 17329333
Ilouze M, Dishon A, Kotler M. Coordinated and sequential transcription of the cyprinid herpesvirus-3 annotated genes. Virus Res. 2012;169:98-106. doi: 10.1016/j.virusres.2012.07.015 PMID: 22841491
Berezikov E, Liu N, Flynt AS, Hodges E, Rooks M, Hannon GJ, et al. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nat Genet. 2010;42:6-9. doi: 10.1038/ng0110-6 PMID: 20037610
Lu J, Shen Y, Carthew RW, Wang SM, Wu C-I. Reply to "Evolutionary flux of canonical microRNAs and mirtrons in Drosophila." Nat Genet. 2010;42:9-10. PMID: 25067898
Lu J, Shen Y, Wu Q, Kumar S, He B, Shi S, et al. The birth and death of microRNA genes in Drosophila. Nat Genet. 2008;40:351-355. doi: 10.1038/ng.73 PMID: 18278047
Cazalla D, Xie M, Steitz JA. A Primate Herpesvirus Uses the Integrator Complex to Generate Viral MicroRNAs. Mol Cell. 2011;43:982-992. doi: 10.1016/j.molcel.2011.07.025 PMID: 21925386
Buck AH, Santoyo-Lopez J, Robertson KA, Kumar DS, Reczko M, Ghazal P. Discrete Clusters of Virus-Encoded MicroRNAs Are Associated with Complementary Strands of the Genome and the 7.2-Kilobase Stable Intron in Murine Cytomegalovirus. J Virol. 2007;81:13761-13770. PMID: 17928340
Umbach JL, Cullen BR. In-depth analysis of Kaposi's sarcoma-associated herpesvirus microRNA expression provides insights into the mammalian microRNA-processing machinery. J Virol. 2010;84:695-703. doi: 10.1128/JVI.02013-09 PMID: 19889781
Yao Y, Zhao Y, Xu H, Smith LP, Lawrie CH, Watson M, et al. MicroRNA Profile of Marek's Disease Virus-Transformed T-Cell Line MSB-1: Predominance of Virus-Encoded MicroRNAs. J Virol. 2008;82:4007-4015. doi: 10.1128/JVI.02659-07 PMID: 18256158
Kuchenbauer F, Morin RD, Argiropoulos B, Petriv OI, Griffith M, Heuser M, et al. In-depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res. 2008;18:1787-1797. doi: 10.1101/gr.077578.108 PMID: 18849523
Meshesha MK, Veksler-Lublinsky I, Isakov O, Reichenstein I, Shomron N, Kedem K, et al. The micro-RNA Transcriptome of Human Cytomegalovirus (HCMV). Open Virol J. 2012;6:38-48. doi: 10.2174/1874357901206010038 PMID: 22715351
Reese TA, Xia J, Johnson LS, Zhou X, Zhang W, Virgin HW. Identification of novel microRNA-like molecules generated from herpesvirus and host tRNA transcripts. J Virol. 2010;84:10344-10353. doi: 10.1128/JVI.00707-10 PMID: 20660200
Chen S-J, Chen G-H, Chen Y-H, Liu C-Y, Chang K-P, Chang Y-S, et al. Characterization of Epstein-Barr Virus miRNAome in Nasopharyngeal Carcinoma by Deep Sequencing. PLoS One. 2010;5:e12745. doi: 10.1371/journal.pone.0012745 PMID: 20862214
Hafner M, Renwick N, Brown M, Mihailović A, Holoch D, Lin C, et al. RNA-ligase-dependent biases in miRNA representation in deep-sequenced small RNA cDNA libraries. RNA. 2011;17:1697-1712. doi: 10.1261/rna.2799511 PMID: 21775473
Sorefan K, Pais H, Hall AE, Kozomara A, Griffiths-Jones S, Moulton V, et al. Reducing ligation bias of small RNAs in libraries for next generation sequencing. Silence. 2012;3:4. doi: 10.1186/1758-907X-3-4 PMID: 22647250
Quail MA, Kozarewa I, Smith F, Scally A, Stephens PJ, Durbin R, et al. A large genome center's improvements to the Illumina sequencing system. Nat Methods. 2008;5:1005-1010. doi: 10.1038/nmeth.1270 PMID: 19034268
Linsen SEV, de Wit E, Janssens G, Heater S, Chapman L, Parkin RK, et al. Limitations and possibilities of small RNA digital gene expression profiling. Nat Methods. 2009;6:474-476. doi: 10.1038/nmeth0709-474 PMID: 19564845
Toedling J, Servant N, Ciaudo C, Farinelli L, Voinnet O, Heard E, et al. Deep-Sequencing Protocols Influence the Results Obtained in Small-RNA Sequencing. PLoS One. 2012;7:e32724. doi: 10.1371/journal.pone.0032724 PMID: 22384282
Wu H, Ye C, Ramirez D, Manjunath N. Alternative processing of primary microRNA transcripts by Drosha generates 50 end variation of mature microRNA. PLoS One. 2009;4:e7566. doi: 10.1371/journal.pone.0007566 PMID: 19859542
Tsutsumi A, Kawamata T, Izumi N, Seitz H, Tomari Y. Recognition of the pre-miRNA structure by Drosophila Dicer-1. Nat Struct Mol Biol. 2011;18:1153-1158. doi: 10.1038/nsmb.2125 PMID: 21926993
Zhang W, Gao S, Zhou X, Xia J, Chellappan P, Zhou X, et al. Multiple distinct small RNAs originate from the same microRNA precursors. Genome Biol. 2010;11:R81. doi: 10.1186/gb-2010-11-8-r81 PMID: 20696037
Wu Y-Q, Chen D-J, He H-B, Chen D-S, Chen L-L, Chen H-C, et al. Pseudorabies Virus Infected Porcine Epithelial Cell Line Generates a Diverse Set of Host MicroRNAs and a Special Cluster of Viral MicroRNAs. PLoS One. 2012;7:e30988. doi: 10.1371/journal.pone.0030988 PMID: 22292087
Yao Y, Smith LP, Petherbridge L, Watson M, Nair V. Novel microRNAs encoded by duck enteritis virus. J Gen Virol. 2012;93:1530-1536. doi: 10.1099/vir.0.040634-0 PMID: 22492913
Zhu JY, Strehle M, Frohn A, Kremmer E, Höfig KP, Meister G, et al. Identification and analysis of expression of novel microRNAs of murine gammaherpesvirus 68. J Virol. 2010;84:10266-10275. doi: 10.1128/JVI.01119-10 PMID: 20668074
Li Y, Zhang Z, Liu F, Vongsangnak W, Jing Q, Shen B. Performance comparison and evaluation of software tools for microRNA deep-sequencing data analysis. Nucl Acids Res. 2012; gks043. doi: 10. 1093/nar/gks043 PMID: 22287634
Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci USA. 2005;102:5570-5575. PMID: 15800047
Glaunsinger BA, Ganem DE. Messenger RNA turnover and its regulation in herpesviral infection. Adv Virus Res. 2006;66:337-394. PMID: 16877064
Jurak I, Kramer MF, Mellor JC, van Lint AL, Roth FP, Knipe DM, et al. Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2. J Virol. 2010;84:4659-4672. doi: 10. 1128/JVI.02725-09 PMID: 20181707
Lin Y-T, Kincaid RP, Arasappan D, Dowd SE, Hunicke-Smith SP, Sullivan CS. Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs. RNA. 2010;16:1540-1558. doi: 10.1261/rna.1967910 PMID: 20566670
Umbach JL, Strelow LI, Wong SW, Cullen BR. Analysis of rhesus rhadinovirus microRNAs expressed in virus-induced tumors from infected rhesus macaques. Virology. 2010;405:592-599. doi: 10.1016/j.virol.2010.06.036 PMID: 20655562
Taft RJ, Simons C, Nahkuri S, Oey H, Korbie DJ, Mercer TR, et al. Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans. Nat Struct Mol Biol. 2010;17:1030-1034. doi: 10.1038/nsmb.1841 PMID: 20622877
Pratt ZL, Kuzembayeva M, Sengupta S, Sugden B. The microRNAs of Epstein-Barr Virus are expressed at dramatically differing levels among cell lines. Virology. 2009;386:387-397. doi: 10.1016/j. virol.2009.01.006 PMID: 19217135
Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog. 2006;2:e23. PMID: 16557291
Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, et al. Prediction and identification of herpes simplex virus 1-encoded microRNAs. J Virol. 2006;80:5499-508. PMID: 16699030
Amen MA, Griffiths A. Identification and Expression Analysis of Herpes B Virus-Encoded Small RNAs. J Virol. 2011;85:7296-7311. doi: 10.1128/JVI.00505-11 PMID: 21543500
Seo GJ, Fink LHL, O'Hara B, Atwood WJ, Sullivan CS. Evolutionarily Conserved Function of a Viral MicroRNA. J Virol. 2008;82:9823-9828. doi: 10.1128/JVI.01144-08 PMID: 18684810
Chen CJ, Kincaid RP, Seo GJ, Bennett MD, Sullivan CS. Insights into Polyomaviridae microRNA function derived from study of the bandicoot papillomatosis carcinomatosis viruses. J Virol. 2011;85:4487-4500. doi: 10.1128/JVI.02557-10 PMID: 21345962
Walz N, Christalla T, Tessmer U, Grundhoff A. A global analysis of evolutionary conservation among known and predicted gammaherpesvirus microRNAs. J Virol. 2010;84:716-728. doi: 10.1128/JVI. 01302-09 PMID: 19889779
Grey F, Hook L, Nelson J. The functions of herpesvirus-encoded microRNAs. Med Microbiol Immunol. 2008;197:261-267. PMID: 18087721
Yao Y, Zhao Y, Xu H, Smith LP, Lawrie CH, Sewer A, et al. Marek's Disease Virus Type 2 (MDV-2) - Encoded MicroRNAs Show No Sequence Conservation with Those Encoded by MDV-1. J Virol. 2007;81:7164-7170. PMID: 17459919
Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769-773. PMID: 15685193
Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455:64-71. doi: 10.1038/nature07242 PMID: 18668037
Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455:58-63. doi: 10.1038/nature07228 PMID: 18668040
Lin H-R, Ganem D. Viral microRNA target allows insight into the role of translation in governing micro-RNA target accessibility. Proc Natl Acad Sci USA. 2011;108:5148-5153. doi: 10.1073/pnas. 1102033108 PMID: 21402938
Tang S, Patel A, Krause PR. Novel Less-Abundant Viral MicroRNAs Encoded by Herpes Simplex Virus 2 Latency-Associated Transcript and Their Roles in Regulating ICP34.5 and ICP0 mRNAs. J Virol. 2009;83:1433-1442. doi: 10.1128/JVI.01723-08 PMID: 19019961
Michel B, Leroy B, Stalin Raj V, Lieffrig F, Mast J, Wattiez R, et al. The genome of cyprinid herpesvirus 3 encodes 40 proteins incorporated in mature virions. J Gen Virol. 2010;91:452-462. doi: 10.1099/vir.0.015198-0 PMID: 19846671
Gu S, Jin L, Zhang F, Sarnow P, Kay MA. Biological basis for restriction of microRNA targets to the 30 untranslated region in mammalian mRNAs. Nat Struct Mol Biol. 2009;16:144-150. doi: 10.1038/nsmb.1552 PMID: 19182800
Penadés JR, Donderis J, García-Caballer M, Tormo-Más MÁ, Marina A. dUTPases, the unexplored family of signalling molecules. Curr Opin Microbiol. 2013;16:163-170. doi: 10.1016/j.mib.2013.02. 005 PMID: 23541339
Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007;26:6133-6140. PMID: 17404574
