Identification and target prediction of miRNAs specifically expressed in rat neural tissue

BackgroundMicroRNAs (miRNAs) are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs.ResultsIn order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values < 0.05. The results indicated that the miRNA profiles were different in neural and non-neural tissues. In total, we found 30 miRNAs that were specifically expressed in neural tissues. For example, miR-199a was specifically expressed in neural tissues. Of these, the expression patterns of four miRNAs were comparable with those of Landgraf et al., Bak et al., and Kapsimani et al. Thirty neural tissue-specific miRNAs were chosen to predict target genes. A total of 1,475 target mRNA were predicted based on the intersection of three public databases, and target mRNA's pathway, function, and regulatory network analysis were performed. We focused on target enrichments of the dorsal root ganglion (DRG) and olfactory bulb. There were four Gene Ontology (GO) functions and five KEGG pathways significantly enriched in DRG. Only one GO function was significantly enriched in the olfactory bulb. These targets are all predictions and have not been experimentally validated.ConclusionOur work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

[1]  Lin Liu,et al.  Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research , 2007, BMC Genomics.

[2]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  A. Silahtaroglu,et al.  MicroRNA expression in the adult mouse central nervous system. , 2008, RNA.

[4]  Gordon K Smyth,et al.  Statistical Applications in Genetics and Molecular Biology Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2011 .

[5]  Yi-xue Li,et al.  Comparison of normalization methods with microRNA microarray. , 2008, Genomics.

[6]  D. Valle,et al.  MicroRNA (miRNA) Transcriptome of Mouse Retina and Identification of a Sensory Organ-specific miRNA Cluster* , 2007, Journal of Biological Chemistry.

[7]  Jian-Fu Chen,et al.  The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation , 2006, Nature Genetics.

[8]  Chaoqian Xu,et al.  The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes , 2007, Journal of Cell Science.

[9]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[10]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[11]  Pasko Rakic,et al.  Microarray analysis of microRNA expression in the developing mammalian brain , 2004, Genome Biology.

[12]  Joshua M. Stuart,et al.  MICROARRAY EXPERIMENTS : APPLICATION TO SPORULATION TIME SERIES , 1999 .

[13]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[14]  Masahiro Sato,et al.  The expression profile of microRNAs in mouse embryos , 2006, Nucleic acids research.

[15]  R. Ravi,et al.  A nearly best-possible approximation algorithm for node-weighted Steiner trees , 1993, IPCO.

[16]  J. Mendell.  MicroRNAs: Critical Regulators of Development, Cellular Physiology and Malignancy , 2005, Cell cycle.

[17]  C. Croce,et al.  MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia , 2007, Oncogene.

[18]  V. Ambros,et al.  Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation , 2004, Genome Biology.

[19]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[20]  Konstantin Khrapko,et al.  A microRNA array reveals extensive regulation of microRNAs during brain development. , 2003, RNA.

[21]  C. Perou,et al.  A custom microarray platform for analysis of microRNA gene expression , 2004, Nature Methods.

[22]  T. Fukushima,et al.  Expression profile analysis of microRNA (miRNA) in mouse central nervous system using a new miRNA detection system that examines hybridization signals at every step of washing. , 2007, Gene.

[23]  Xiaowei Wang,et al.  Systematic identification of microRNA functions by combining target prediction and expression profiling , 2006, Nucleic acids research.

[24]  M. Levine,et al.  Spatial regulation of microRNA gene expression in the Drosophila embryo. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[26]  B. Reinhart,et al.  MicroRNAs in plants. , 2002, Genes & development.

[27]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[28]  Stephen W. Wilson,et al.  MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system , 2007, Genome Biology.

[29]  Xu Ma,et al.  Genome-wide microRNA profiling in human fetal nervous tissues by oligonucleotide microarray , 2006, Child's Nervous System.