Human microRNA targets Journal Article
| Authors: | John, B.; Enright, A. J.; Aravin, A.; Tuschl, T.; Sander, C.; Marks, D. S. |
| Article Title: | Human microRNA targets |
| Abstract: | MicroRNAs (miRNAs) interact with target mRNAs at specific sites to induce cleavage of the message or inhibit translation. The specific function of most mammalian miRNAs is unknown. We have predicted target sites on the 3′ untranslated regions of human gene transcripts for all currently known 218 mammalian miRNAs to facilitate focused experiments. We report about 2,000 human genes with miRNA target sites conserved in mammals and about 250 human genes conserved as targets between mammals and fish. The prediction algorithm optimizes sequence complementarity using position-specific rules and relies on strict requirements of interspecies conservation. Experimental support for the validity of the method comes from known targets and from strong enrichment of predicted targets in mRNAs associated with the fragile X mental retardation protein in mammals. This is consistent with the hypothesis that miRNAs act as sequence-specific adaptors in the interaction of ribonuclear particles with translationally regulated messages. Overrepresented groups of targets include mRNAs coding for transcription factors, components of the miRNA machinery, and other proteins involved in translational regulation, as well as components of the ubiquitin machinery, representing novel feedback loops in gene regulation. Detailed information about target genes, target processes, and open-source software for target prediction (miRanda) is available at http://www.microrna. org. Our analysis suggests that miRNA genes, which are about 1% of all human genes, regulate protein production for 10% or more of all human genes. Copyright: © 2004 John et al. |
| Keywords: | genetics; molecular genetics; methodology; ubiquitin; protein motif; animal; metabolism; mammalia; animals; gene targeting; microrna; biological model; biology; computational biology; protein targeting; protein binding; membrane proteins; intron; introns; transcription factor; algorithms; rna; gene expression regulation; chemistry; conserved sequence; molecular sequence data; algorithm; messenger rna; protein synthesis; rna, messenger; models, statistical; signal peptide; intracellular signaling peptides and proteins; mammal; nucleotide sequence; membrane protein; rat; rna translation; protein biosynthesis; gene control; models, genetic; protein structure, tertiary; rats; 3' untranslated region; gene silencing; micrornas; fish; computer program; software; statistical model; genetic code; protein tertiary structure; genetic conservation; complementary dna; amino acid motifs; amyloid precursor protein; chromosome map; chromosome mapping; 3' untranslated regions; rna sequence; dna, complementary; hypothesis; protein synthesis regulation; adaptor protein; amyloid beta-protein precursor; polyadenylation; translation regulation; ribonucleoprotein; fragile x mental retardation protein; humans; human; article; dlg4 protein, human |
| Journal Title: | PLoS Biology |
| Volume: | 2 |
| Issue: | 11 |
| ISSN: | 1544-9173 |
| Publisher: | Public Library of Science |
| Date Published: | 2004-10-05 |
| Start Page: | e363 |
| Language: | English |
| DOI: | 10.1371/journal.pbio.0020363 |
| PROVIDER: | scopus |
| PMCID: | PMC521178 |
| PUBMED: | 15502875 |
| DOI/URL: | |
| Notes: | PloS Biol. -- Cited By (since 1996):1341 -- Export Date: 16 June 2014 -- CODEN: PBLIB -- Source: Scopus |
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