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.

Upregulation of miR-21 by Ras in vivo and its role in tumor growth

“…The network building algorithm predicts that its regulatory signaling interaction network is significantly downregulated by the overexpression of miR-21. CKS2, a MIRANDA algorithm-predicted miR-21 target (John et al, 2004), is known to regulate Cyclin B1 in human (Martinsson-Ahlzen et al, 2008). Cyclin B1 is downregulated and contributes to the enrichment of the cell cycle GO category.…”

“…Cyclin B1 is known to be expressed predominantly in the G2/M phase of cell division (Pines and Hunter, 1989). Finally the hub UBE2 complex contains both downregulated genes and predicted mir-21 targets according to the PITA algorithm (John et al, 2004;Kertesz et al, 2007).…”

Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells

“…Here, bioinformatic analysis was performed on these mRNA and protein targets using microRNA.org: A resource for predicted microRNA targets and expression, based on the miRanda algorithm (http://www.microrna.org/microrna/home.do) [30,31] to determine if they could potentially be regulated by the miRNAs identified as of interest in this study. A large number of these mRNAs were found to contain putative binding sites for the target ACCEPTED MANUSCRIPT 9 miRNAs, including several mRNAs of which could potentially be targeted by more than one of the identified miRNAs (Table 3).…”

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

“…Computational algorithms, including our own, to predict target genes for miRNAs, identified Mad as a potential target of ban (TargetScan, miRanda) [20,71] which was subsequently validated by our group in vitro in Drosophila S2 cells [22]. We find two putative ban binding sites in the Mad 3ʹUTR (Fig.…”