Genome-wide and species-wide in silico screening for intragenic MicroRNAs in human, mouse and chicken

PLoS One. 2013 Jun 6;8(6):e65165. doi: 10.1371/journal.pone.0065165. Print 2013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Chickens / genetics*
  • Computer Simulation*
  • Conserved Sequence
  • Databases, Genetic
  • Exons
  • Gene Expression Regulation
  • Genome*
  • Humans
  • Introns
  • Mice
  • MicroRNAs / classification
  • MicroRNAs / genetics*
  • Molecular Sequence Annotation
  • Molecular Sequence Data
  • Open Reading Frames*
  • RNA, Messenger / genetics*

Substances

  • MicroRNAs
  • RNA, Messenger

Grants and funding

This work was supported by the Slovenian Research Agency (ARRS) through the Research programme Comparative genomics and genome biodiversity [grant number P4–0220]. GAC is supported as a Fellow at The University of Texas M. D. Anderson Research Trust, as a Fellow of The University of Texas System Regents Research Scholar, and by the CLL Global Research Foundation. Work in Dr. Calin’s laboratory is supported in part by National Institutes of Health, by Department of Defense, by Developmental Research Awards in Breast Cancer, Ovarian Cancer and Leukemia SPOREs, and by 2009 Seena Magowitz - Pancreatic Cancer Action Network - AACR Pilot Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.