Probing microRNAs with microarrays: tissue specificity and functional inference.

MicroRNAs (miRNAs) are short, stable, noncoding RNAs involved in post-transcriptional gene silencing via hybridization to mRNA. Few have been thoroughly characterized in any species. Here, we describe a method to detect miRNAs using micro-arrays, in which the miRNAs are directly hybridized to the array. We used this method to analyze miRNA expression across 17 mouse organs and tissues. More than half of the 78 miRNAs detected were expressed in specific adult tissues, suggesting that miRNAs have widespread regulatory roles in adults. By comparing miRNA levels to mRNA levels determined in a parallel microarray analysis of the same tissues, we found that the expression of target mRNAs predicted on the basis of sequence complementarity is unrelated to the tissues in which the corresponding miRNA is expressed.

[1]  J. Wiegant,et al.  ULS: a versatile method of labeling nucleic acids for FISH based on a monofunctional reaction of cisplatin derivatives with guanine moieties , 1999, Cytogenetic and Genome Research.

[2]  Gary Ruvkun,et al.  Identification of many microRNAs that copurify with polyribosomes in mammalian neurons , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  N. Perrone-Bizzozero,et al.  Role of HuD and other RNA‐binding proteins in neural development and plasticity , 2002, Journal of neuroscience research.

[4]  Sarah Olson,et al.  Quantitation of microRNAs using a modified Invader assay. , 2004, RNA.

[5]  Brendan J. Frey,et al.  A Panoramic View of Yeast Noncoding RNA Processing , 2003, Cell.

[6]  Ricardo Baeza-Yates,et al.  Information Retrieval: Data Structures and Algorithms , 1992 .

[7]  T. Tuschl,et al.  New microRNAs from mouse and human. , 2003, RNA.

[8]  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.

[9]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[10]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[11]  Seungyoon Nam,et al.  Prediction of Mammalian MicroRNA Targets - Comparative Genomics Approach with Longer 3' UTR Databases , 2005 .

[12]  Brendan J. Frey,et al.  Spatial Bias Removal in Microarray Images , 2003 .

[13]  T. Tuschl,et al.  Identification of Tissue-Specific MicroRNAs from Mouse , 2002, Current Biology.

[14]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[15]  R. Plasterk,et al.  Dicers at RISC The Mechanism of RNAi , 2004, Cell.

[16]  G. Ruvkun,et al.  A uniform system for microRNA annotation. , 2003, RNA.

[17]  D Haussler,et al.  Knowledge-based analysis of microarray gene expression data by using support vector machines. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Schuman,et al.  Regulation and function of local protein synthesis in neuronal dendrites. , 2002, Trends in biochemical sciences.

[19]  Yudong D. He,et al.  Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer , 2001, Nature Biotechnology.

[20]  C. Burge,et al.  Vertebrate MicroRNA Genes , 2003, Science.

[21]  K. Czaplinski,et al.  Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. , 2004, RNA.

[22]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[23]  Qian Liu,et al.  A high-throughput method to monitor the expression of microRNA precursors. , 2004, Nucleic acids research.

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

[25]  Martin Vingron,et al.  Variance stabilization applied to microarray data calibration and to the quantification of differential expression , 2002, ISMB.

[26]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[27]  H. Lipkin.  Where is the ?c? , 1978 .

[28]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

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

[30]  Generation of a catalytic module on a self-folding RNA. , 2004, RNA.

[31]  P. Sharp,et al.  Embryonic stem cell-specific MicroRNAs. , 2003, Developmental cell.

[32]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[33]  C. Croce,et al.  An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[35]  U. Kutay,et al.  Nuclear Export of MicroRNA Precursors , 2004, Science.