Bino John1, Anton J. Enright1,2, Alexei Aravin3, Thomas Tuschl3, Chris Sander1, Debora S. Marks4*
1 Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America,, 2 Wellcome Trust Sanger Institute, Cambridge, United Kingdom,, 3 Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York, United States of America,, 4 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America
*To whom correspondence should be addressed. E-mail: email@example.com
Academic Editor: James C. Carrington, Oregon State University
Received: May 18, 2004; Accepted: August 20, 2004; Published: October 5, 2004
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.
Abbreviations: AGO, Argonaute; APP, amyloid precursor protein; CPE, cytoplasmic polyadenylation element; CPEB, cytoplasmic polyadenylation binding protein; FMRP, fragile X mental retardation protein; GO, Gene Ontology; miRNA, microRNA; nt, nucleotide; PSD95, postsynaptic density protein 95; RISC, RNA-induced silencing complex; RNP, ribonuclear particle; siRNA, small interfering RNA; UTR, untranslated region
Source: PLoS Biol 2(11): e363. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.