title: Fluctuation of global gene expression by endogenous miRNA response to the introduction of an exogenous miRNA.
abstract: Most of the intracellular endogenous microRNAs (endo-miRNAs) are considered to be saturated in Argonaute (Ago) proteins in the RNA-induced silencing complexes (RISCs). When exogenous miRNAs (exo-miRNAs) are introduced into cells, endo-miRNAs in the RISC may be replaced with exo-miRNAs or exo-miRNAs, and endo-miRNAs might also compete for the position in the newly synthesized RISC with each other. This would lead to the fluctuation of global gene expression not only by repression of exo-miRNA target gene expression, but also by the increase of the endo-miRNA target gene expression. In the present study, we quantified the changes in the expression levels of target genes of exo-miRNA and endo-miRNA in the cells transfected with fifteen different exo-miRNAs by microarray experiments. Different exo-miRNAs increased ratios of expression levels of target genes of a given endo-miRNA to different extents, suggesting that the replacement efficiencies might differ according to the exo-miRNA types. However, the increased ratios in the expression levels of each endo-miRNA target genes by the transfection of any particular exo-miRNA were mostly equivalent, suggesting that the endo-miRNAs present in the RISC might be replaced with excessive exo-miRNAs at similar levels, probably because they exist in single-stranded forms in the RISC.
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba-ken 277-8561, Japan. ktei@bi.s.u-tokyo.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nagata
authors.forename: Eigo
authors.initials: E
authors.lastname: Shimizu
authors.forename: Naoki
authors.initials: N
authors.lastname: Hibio
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ui-Tei
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D034743:RNA-Induced Silencing Complex; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; D008156:Luciferases