Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets
Open accessAbstract
We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An overrepresentation of conserved adenosines flanking the seed complementary sites in mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of our gene set. Targeting was also detected in open reading frames. In sum, well over one third of human genes appear to be conserved miRNA targets.
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STAT3 is negatively regulated by miR-21 according to the microarray data and is a predicted miR-21 target.
“STAT3, the other gene that may play a tumor suppressor function in GBM (11), is also negatively regulated by miR-21 according to the microarray data (see Table S1 in the supplemental material) and is a predicted miR-21 target (29, 34).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [34]
Most animal miRNAs pair to the 3' UTRs of their targets by incomplete base-pairing, in which nucleotides 2-7 of the mature miRNA sequence, the seed region, appear critical for target site recognition.
“While plant miRNAs are generally perfectly complementary to their target mRNAs, most animal miRNAs pair to the 39 UTRs of their targets by incomplete base-pairing, in which nucleotides 2-7 of the mature miRNA sequence, termed the seed region, appear to be critical for target site recognition (Lewis et al. 2005).”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Lewis et al. 2005
The 3'UTR of the NR2A subunit of NMDA receptors contains a conserved sequence complementary to the seed region of miR-125b.
“For example, the 3’UTR of the NR2A subunit of NMDA receptors contains such a conserved sequence complementary to the seed region of miR-125b (Figure 6A).”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Lewis et al., 2005
It is very likely that most miRNAs have many, perhaps as many as a few thousand, mRNA targets.
“We also find that neurons express multiple miRNAs and it is very likely that most miRNAs have many, perhaps as many as a few thousand, mRNA targets [1,2,6,56].”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [1]
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MicroRNA Expression Aberration as Potential Peripheral Blood Biomarkers for Schizophrenia
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microRNA strand selection: Unwinding the rules
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An updated role of microRNA-124 in central nervous system disorders: a review
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An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model
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Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain
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“…of Medicine, Washington University School of Medicine, St. Louis, United States; 6Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; 7Department of Biostatistics, Fielding School of Public Health, University of”
BackgroundHuman Argonaute 2 Has diverse reaction pathways on Target RNAs
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MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-κB-TNFα pathway
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MicroRNAs in placental health and disease
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Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder
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Regulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma
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- Authors
- Lewis, B. P., Burge, C. B., & Bartel, D. P.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Burge, Christopher B.
- Bartel, David P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 120
- Issue
- 1
- Pages
- 15-20
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2083381199
- Cited by
- 11,855
- References
- 0
- Citations by year
- 2026: 142 · 2025: 187 · 2024: 270 · 2023: 358 · 2022: 391 · 2021: 536 · 2020: 525 · 2019: 596 · 2018: 688 · 2017: 712 · 2016: 811 · 2015: 904 · 2014: 927 · 2013: 980 · 2012: 845
- FWCI
- 123.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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
- miRNA target prediction, miRNA seed sequence, 3' untranslated region, open reading frames
- MeSH terms
- Adenosine, Amino Acid Sequence, Animals, Chickens, Dogs, Gene Expression Regulation, Humans, Molecular Sequence Data, Nucleic Acid Hybridization, Nucleotides, RNA, Messenger, Gene Targeting, 3' Untranslated Regions, MicroRNAs, Mice, Rats
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