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Updated: Feb 10, 2026
An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
Human microRNAs preferentially target genes with intermediate levels of expression and its formation by mammalian
Hisakazu Iwama1, Kiyohito Kato2, Hitomi Imachi3
1Life Science Research Center, Kagawa University, Ikenobe, Miki-cho, Kita-gun, Kagawa, Japan.
Abstract:
MicroRNAs (miRNAs) are short, endogenous RNAs that post-transcriptionally repress mRNAs. Over the course of evolution, many new miRNAs are known to have emerged and added to the existing miRNA repertoires of drosophilids and vertebrates. Despite the large number of miRNAs in existence, the complementary pairing of only ~7 bases between miRNAs and mRNAs is sufficient to induce repression. Thus, miRNA targeting is so widespread that genes coexpressed with a miRNA have evolved to avoid sites that are targeted by the miRNA. Besides this avoidance, little is known about the preferential modes of miRNA targeting. Therefore, to elucidate miRNA targeting preference and avoidance, we evaluated the bias of the number of miRNA targeting occurrences in relation to expression intensities of miRNAs and their coexpressed target mRNAs by surveying transcriptome data from human organs. We found that miRNAs preferentially target genes with intermediate levels of expression, while avoiding highly expressed ones, and that older miRNAs have greater targeting specificity, suggesting that specificity increases during the course of evolution.
Insights
MicroRNAs (miRNAs) target genes with intermediate expression levels, avoiding highly expressed ones. Older miRNAs exhibit greater targeting specificity, indicating increased precision during evolution.
Area of Science:
- Molecular Biology
- Genetics
- Bioinformatics
Background:
- MicroRNAs (miRNAs) are short, endogenous RNA molecules regulating gene expression post-transcriptionally.
- New miRNAs have emerged throughout evolution, expanding miRNA repertoires in various species.
- Efficient gene repression occurs with minimal miRNA-mRNA base pairing (~7 nucleotides).
Purpose of the Study:
- To investigate miRNA targeting preferences and avoidance mechanisms.
- To analyze the relationship between miRNA targeting frequency and expression levels of miRNAs and their coexpressed target mRNAs.
- To understand how miRNA targeting specificity evolves over time.
Main Methods:
- Surveyed human organ transcriptome data.
- Evaluated the bias in miRNA targeting occurrences.
- Correlated targeting with expression intensities of miRNAs and coexpressed target mRNAs.
Main Results:
- MicroRNAs preferentially target genes with intermediate expression levels.
- Highly expressed genes are avoided by miRNA targeting.
- Older miRNAs demonstrate a higher degree of targeting specificity.
Conclusions:
- MiRNA targeting is biased towards genes with moderate expression.
- Evolutionary processes appear to refine miRNA targeting specificity.
- Specificity in miRNA targeting increases as miRNAs age over evolutionary timescales.
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