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.
authors.affiliation: Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Bino
authors.initials: B
authors.lastname: John
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.forename: Alexei
authors.initials: A
authors.lastname: Aravin
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Debora S
authors.initials: DS
authors.lastname: Marks
mesh_terms: D020413:3' Untranslated Regions; D000465:Algorithms; D020816:Amino Acid Motifs; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D007438:Introns; D008565:Membrane Proteins / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry*; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D026723:Polyadenylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012984:Software
chemical_list: D020413:3' Untranslated Regions; D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D000076122:Disks Large Homolog 4 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D012313:RNA; D012333:RNA, Messenger; C501444:DLG4 protein, human