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Cited by 311MicroRNA in disease regulationPlant Molecular Biology ResearchRNA Research and Splicing

Transcriptome-wide miR-155 Binding Map Reveals Widespread Noncanonical MicroRNA Targeting

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Loeb, Gabriel B., Khan, Aly A., Canner, David, Hiatt, Joseph B., Shendure, Jay, Darnell, Robert B., Leslie, Christina S., Rudensky, Alexander Y.·2012·Molecular Cell
DOI 10.1016/j.molcel.2012.10.002PMC PMC3562697
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Abstract

MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA-miR-155-in a genetically controlled manner. We found that approximately 40% of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these noncanonical sites feature extensive complementarity to the miRNA seed with one mismatch. These noncanonical sites confer regulation of gene expression, albeit less potently than canonical sites. Thus, noncanonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation.

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    “What is more, a single microRNA may target different genes involved in a single biological process [11], potentially leading to significant changes in cell function.”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [11]

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Cited by

Sorted by citations

Authors
Loeb, G. B., Khan, A. A., Canner, D., Hiatt, J. B., Shendure, J., Darnell, R. B., Leslie, C. S., & Rudensky, A. Y.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Washington (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Rudensky, Alexander Y.
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2012-12
Volume
48
Issue
5
Pages
760-770
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2012.10.002
PMC
PMC3562697
OpenAlex
W2078657796
Cited by
311
References
2
Citations by year
2026: 7 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 21 · 2020: 18 · 2019: 23 · 2018: 26 · 2017: 31 · 2016: 38 · 2015: 32 · 2014: 46 · 2013: 29 · 2012: 1
FWCI
10.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of General Medical Sciences (GM 07739, T32GM007739)
  • National Institute of Allergy and Infectious Diseases (R37AI034206)
  • National Institute of Neurological Disorders and Stroke (R01NS081706)
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
miR-155, miRNA target identification, gene expression regulation, 3' untranslated region
MeSH terms
Animals, Binding Sites, Humans, Lymphocyte Activation, RNA, Messenger, Transfection, CD4-Positive T-Lymphocytes, Down-Regulation, Polymerase Chain Reaction, Genes, Reporter, Mice, Knockout, Computational Biology, Oligonucleotide Array Sequence Analysis, 3' Untranslated Regions, Gene Expression Profiling, MicroRNAs, Mice, HEK293 Cells, Nucleotide Motifs, Transcriptome, Argonaute Proteins

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