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Cited by 3,796MicroRNA in disease regulationPlant Molecular Biology ResearchRNA Research and Splicing

Human MicroRNA Targets

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John, Bino, Enright, Anton J, Aravin, Alexei, Tuschl, Thomas, Sander, Chris, Marks, Debora S·2004·PLoS Biology
DOI 10.1371/journal.pbio.0020363PMC PMC521178
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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.

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  • Human genes with predicted miRNA targets appear to be somewhat enriched for 3'-UTR HCEs; examples include EIF4E, MECP, MYC, MYCN, NBPHOX, and UBE3A.

    “Human genes with predicted miRNA targets appear to be somewhat enriched for 3Ј-UTR HCEs; examples include the genes for the eukaryotic translation initiation factor EIF4E, the methyl CpG-binding protein MECP, the DNA-binding proteins (and oncoproteins) MYC and MYCN, the homeobox protein NBPHOX, and the ubiquitin protein ligase UBE3A, which is mutated in Angelman syndrome (John et al. 2004).”

    From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as John et al. 2004

    The Results (Overview of Mammalian miRNA Target Genes; page unavailable) report predicted human miRNA targets with conserved sites in their 3′ UTRs, and the Results (Components of RNPs Regulated by miRNAs; page unavailable) name c-myc as a predicted target. Our copy does not report enrichment of predicted target genes for 3′-UTR HCEs or substantiate the full list of examples in the claim. (LLM, conf=0.81)

    Experimental — accuracy not yet measured

  • John et al. found a substantial enrichment for predicted miRNA targets among the genes for FMR1, the ELAV-like proteins, and the polyadenylation-binding proteins (CPEBs), and among the genes whose mRNAs are known to be bound by these proteins.

    “John et al. (2004) found a substantial enrichment for predicted miRNA targets among the genes for the fragile X mental retardation protein FMR1, the ELAV-like proteins, and the polyadenylation-binding proteins (CPEBs), and among the genes whose mRNAs are known to be bound by these proteins, suggesting that miRNAs play a critical role in the regulatory networks in which these genes participate.”

    From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as John et al. 2004

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Cited by

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Authors
John, B., Enright, A. J., Aravin, A., Tuschl, T., Sander, C., & Marks, D. S.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Rockefeller University (US)
  • Harvard University (US)
Corresponding author
Marks, Debora S
ORCID
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2004-10-05
Volume
2
Issue
11
Pages
e363
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.0020363
PMC
PMC521178
OpenAlex
W2040191060
Cited by
3,796
References
7
Citations by year
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FWCI
44.50
Type
journal article
Language
en
Update notices
correction (2005-07-12)
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Apollo (cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
microRNA binding sites, miRNA target prediction, 3' untranslated region, sequence complementarity, interspecies conservation, Miranda, FMRP, translational regulation, transcription factors, gene expression regulation
MeSH terms
Disks Large Homolog 4 Protein, Algorithms, Animals, Chromosome Mapping, Gene Expression Regulation, Humans, Introns, Membrane Proteins, Models, Genetic, Molecular Sequence Data, Protein Binding, RNA, RNA, Messenger, Software, Protein Biosynthesis, Models, Statistical, Amyloid beta-Protein Precursor, Conserved Sequence, Protein Structure, Tertiary, DNA, Complementary, Computational Biology, 3' Untranslated Regions, Amino Acid Motifs, Gene Silencing, Polyadenylation, MicroRNAs, Intracellular Signaling Peptides and Proteins, Rats, Fragile X Messenger Ribonucleoprotein 1

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