title: Genome-wide and species-wide in silico screening for intragenic MicroRNAs in human, mouse and chicken.
abstract: MicroRNAs (miRNAs) are non-coding RNAs (ncRNAs) involved in regulation of gene expression. Intragenic miRNAs, especially those exhibiting a high degree of evolutionary conservation, have been shown to be coordinately regulated and/or expressed with their host genes, either with synergistic or antagonistic correlation patterns. However, the degree of cross-species conservation of miRNA/host gene co-location is not known and co-expression information is incomplete and fragmented among several studies. Using the genomic resources (miRBase and Ensembl) we performed a genome-wide in silico screening (GWISS) for miRNA/host gene pairs in three well-annotated vertebrate species: human, mouse, and chicken. Approximately half of currently annotated miRNA genes resided within host genes: 53.0% (849/1,600) in human, 48.8% (418/855) in mouse, and 42.0% (210/499) in chicken, which we present in a central publicly available Catalog of intragenic miRNAs (http://www.integratomics-time.com/miR-host/catalog). The miRNA genes resided within either protein-coding or ncRNA genes, which include long intergenic ncRNAs (lincRNAs) and small nucleolar RNAs (snoRNAs). Twenty-seven miRNA genes were found to be located within the same host genes in all three species and the data integration from literature and databases showed that most (26/27) have been found to be co-expressed. Particularly interesting are miRNA genes located within genes encoding for miRNA silencing machinery (DGCR8, DICER1, and SND1 in human and Cnot3, Gdcr8, Eif4e, Tnrc6b, and Xpo5 in mouse). We furthermore discuss a potential for phenotype misattribution of miRNA host gene polymorphism or gene modification studies due to possible collateral effects on miRNAs hosted within them. In conclusion, the catalog of intragenic miRNAs and identified 27 miRNA/host gene pairs with cross-species conserved co-location, co-expression, and potential co-regulation, provide excellent candidates for further functional annotation of intragenic miRNAs in health and disease.
authors.affiliation: Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia.
authors.forename: Irena
authors.initials: I
authors.lastname: Godnic
authors.forename: Minja
authors.initials: M
authors.lastname: Zorc
authors.forename: Dasa
authors.initials: D
authors.lastname: Jevsinek Skok
authors.forename: George Adrian
authors.initials: GA
authors.lastname: Calin
authors.forename: Simon
authors.initials: S
authors.lastname: Horvat
authors.forename: Peter
authors.initials: P
authors.lastname: Dovc
authors.forename: Milena
authors.initials: M
authors.lastname: Kovac
authors.forename: Tanja
authors.initials: T
authors.lastname: Kunej
mesh_terms: D000818:Animals; D001483:Base Sequence; D002645:Chickens / Q000235:genetics*; D003198:Computer Simulation; D017124:Conserved Sequence; D030541:Databases, Genetic; D005091:Exons; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D007438:Introns; D051379:Mice; D035683:MicroRNAs / Q000145:classification / Q000235:genetics*; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger