Repertoire of Bovine miRNA and miRNA-Like Small Regulatory RNAs Expressed upon Viral Infection

MicroRNA (miRNA) and other types of small regulatory RNAs play a crucial role in the regulation of gene expression in eukaryotes. Several distinct classes of small regulatory RNAs have been discovered in recent years. To extend the repertoire of small RNAs characterized in mammals and to examine relationship between host miRNA expression and viral infection we used Illumina's ultrahigh throughput sequencing approach. We sequenced three small RNA libraries prepared from cell line derived from the adult bovine kidney under normal conditions and upon infection of the cell line with Bovine herpesvirus 1. We used a bioinformatics approach to distinguish authentic mature miRNA sequences from other classes of small RNAs and short RNA fragments represented in the sequencing data. Using this approach we detected 219 out of 356 known bovine miRNAs and 115 respective miRNA* sequences. In addition we identified five new bovine orthologs of known mammalian miRNAs and discovered 268 new cow miRNAs many of which are not identifiable in other mammalian genomes and thus might be specific to the ruminant lineage. In addition we found seven new bovine mirtron candidates. We also discovered 10 small nucleolar RNA (snoRNA) loci that give rise to small RNA with possible miRNA-like function. Results presented in this study extend our knowledge of the biology and evolution of small regulatory RNAs in mammals and illuminate mechanisms of small RNA biogenesis and function. New miRNA sequences and the original sequencing data have been submitted to miRNA repository (miRBase) and NCBI GEO archive respectively. We envisage that these resources will facilitate functional annotation of the bovine genome and promote further functional and comparative genomics studies of small regulatory RNA in mammals.

[1]  S H MADIN,et al.  Established Kidney Cell Lines of Normal Adult Bovine and Ovine Origin.∗ , 1958, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[2]  Timothy P. L. Smith,et al.  Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues. , 2007, Physiological genomics.

[3]  W. Bender,et al.  MicroRNAs in the Drosophila bithorax complex. , 2008, Genes & development.

[4]  Marwan Shinawi,et al.  Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster , 2008, Nature Genetics.

[5]  David Haussler,et al.  The UCSC genome browser database: update 2007 , 2006, Nucleic Acids Res..

[6]  Ashesh A. Saraiya,et al.  snoRNA, a Novel Precursor of microRNA in Giardia lamblia , 2008, PLoS pathogens.

[7]  N. Perrimon,et al.  An endogenous small interfering RNA pathway in Drosophila , 2008, Nature.

[8]  Robert J. Moore,et al.  A microRNA catalog of the developing chicken embryo identified by a deep sequencing approach. , 2008, Genome research.

[9]  Y. Sakaki,et al.  Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes , 2008, Nature.

[10]  F. Strozzi,et al.  Annotation of 390 bovine miRNA genes by sequence similarity with other species. , 2009, Animal Genetics.

[11]  David P. Bartel,et al.  Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals , 2008, Nature.

[12]  R. Terns,et al.  Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs , 2007, Nature Reviews Molecular Cell Biology.

[13]  P. Stadler,et al.  RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription , 2007, Science.

[14]  Manolis Kellis,et al.  A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands. , 2008, Genes & development.

[15]  Christopher M. Player,et al.  Large-Scale Sequencing Reveals 21U-RNAs and Additional MicroRNAs and Endogenous siRNAs in C. elegans , 2006, Cell.

[16]  A. Hüttenhofer,et al.  Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Brosius,et al.  Deletion of the MBII-85 snoRNA Gene Cluster in Mice Results in Postnatal Growth Retardation , 2007, PLoS genetics.

[18]  T. Du,et al.  Asymmetry in the Assembly of the RNAi Enzyme Complex , 2003, Cell.

[19]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[20]  M. Stephens,et al.  RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. , 2008, Genome research.

[21]  R. Aharonov,et al.  Identification of hundreds of conserved and nonconserved human microRNAs , 2005, Nature Genetics.

[22]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[23]  Christoph Flamm,et al.  The expansion of the metazoan microRNA repertoire , 2006, BMC Genomics.

[24]  Mary Goldman,et al.  The UCSC Genome Browser database: update 2011 , 2010, Nucleic Acids Res..

[25]  E. Lai,et al.  The Mirtron Pathway Generates microRNA-Class Regulatory RNAs in Drosophila , 2007, Cell.

[26]  Affymetrix Encode Transcriptome Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs. , 2009 .

[27]  A. Hüttenhofer,et al.  The expanding snoRNA world. , 2002, Biochimie.

[28]  James C. Carrington,et al.  Specialization and evolution of endogenous small RNA pathways , 2007, Nature Reviews Genetics.

[29]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[30]  R. Gregory,et al.  Many roads to maturity: microRNA biogenesis pathways and their regulation , 2009, Nature Cell Biology.

[31]  D. Bartel,et al.  Intronic microRNA precursors that bypass Drosha processing , 2007, Nature.

[32]  J. Kawai,et al.  Tiny RNAs associated with transcription start sites in animals , 2009, Nature Genetics.

[33]  Terrence S. Furey,et al.  The UCSC Genome Browser Database: update 2006 , 2005, Nucleic Acids Res..

[34]  Hanah Margalit,et al.  Clustering and conservation patterns of human microRNAs , 2005, Nucleic acids research.

[35]  Lin He,et al.  MicroRNAs: small RNAs with a big role in gene regulation , 2004, Nature reviews genetics.

[36]  Honglin Jiang,et al.  Identification and characterization of microRNAs from the bovine adipose tissue and mammary gland , 2007, FEBS letters.

[37]  Eugene Berezikov,et al.  Mammalian mirtron genes. , 2007, Molecular cell.

[38]  Eugene Berezikov,et al.  Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci. , 2008, Genes & development.

[39]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[40]  Sean McWilliam,et al.  Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. , 2008, Molecular biology and evolution.

[41]  Edwin Cuppen,et al.  Diversity of microRNAs in human and chimpanzee brain , 2006, Nature Genetics.

[42]  F. McCarthy,et al.  Construction and Manipulation of an Infectious Clone of the Bovine Herpesvirus 1 Genome Maintained as a Bacterial Artificial Chromosome , 2002, Journal of Virology.

[43]  Manolis Kellis,et al.  Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs. , 2007, Genome research.

[44]  Ryan D. Morin,et al.  Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. , 2008, Genome research.

[45]  Robert Blelloch,et al.  Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. , 2008, Genes & development.

[46]  Martin J. Simard,et al.  Argonaute proteins: key players in RNA silencing , 2008, Nature Reviews Molecular Cell Biology.

[47]  Terrence S. Furey,et al.  The UCSC Genome Browser Database , 2003, Nucleic Acids Res..

[48]  K. Worley,et al.  The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution , 2009, Science.

[49]  P. Zamore,et al.  Small silencing RNAs: an expanding universe , 2009, Nature Reviews Genetics.

[50]  J. Mattick,et al.  Small RNAs derived from snoRNAs. , 2009, RNA.

[51]  D. Marks,et al.  The small RNA profile during Drosophila melanogaster development. , 2003, Developmental cell.

[52]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[53]  N. Rajewsky,et al.  A human snoRNA with microRNA-like functions. , 2008, Molecular cell.