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Updated: Apr 25, 2026
A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
Published on: June 16, 2022
CPuORF correlates with miRNA responsive elements on protein evolutionary rates
Wangxiong Hu1, Tingzhang Wang2, Yanmei Yang3
1College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China; Cancer Institute, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Abstract:
miRNA is increasingly being recognized as a key regulator of metabolism in animals. A wealth of evidence has suggested that miRNA mainly binds 3' UTR of mRNA and modulates the cell activities via repressing the mRNA translation. However, as the translation initiates at 5' UTR, cis elements like upstream open reading frame (uORF) resided in 5' UTR may also affect the translation efficiency or elongation. In this study, we performed a systematic analysis of miRNA responsive elements (MREs) and uORF of the same transcript in three model organisms (human, mouse, and Drosophila). Intriguingly, we found that the 3' UTR length grew with the complexity of species (human>mouse>Drosophila), in sharp contrast with the invariability of 5' UTR. Additionally, MRE number correlated well with the 3' UTR length, while uORF number showed a weak correlation with the 5' UTR length. Further, we found that human genes with conserved peptide upstream open reading frame (CPuORF) tend to have more MREs and lower evolutionary rates, which provides new insights into the correlation between UTR properties and translational control in animals.
Insights
MicroRNAs (miRNAs) regulate animal metabolism by binding mRNA. This study reveals 3' untranslated region (UTR) length varies by species complexity, impacting miRNA binding and translation efficiency.
Area of Science:
- Molecular Biology
- Genetics
- Evolutionary Biology
Background:
- MicroRNAs (miRNAs) are crucial regulators of animal metabolism.
- miRNAs primarily target the 3' untranslated region (UTR) of messenger RNA (mRNA) to repress translation.
- The 5' UTR, containing elements like upstream open reading frames (uORFs), also influences translation initiation and efficiency.
Purpose of the Study:
- To systematically analyze miRNA responsive elements (MREs) and uORFs in the same transcripts across human, mouse, and Drosophila.
- To investigate the relationship between UTR properties, species complexity, and translational control mechanisms.
Main Methods:
- Comparative analysis of 3' UTR length, 5' UTR length, MREs, and uORFs in human, mouse, and Drosophila.
- Correlation analysis between UTR characteristics and species complexity.
- Examination of conserved peptide upstream open reading frames (CPuORFs) and their association with MREs and evolutionary rates.
Main Results:
- 3' UTR length increases with species complexity (human > mouse > Drosophila), while 5' UTR length remains relatively invariant.
- The number of MREs strongly correlates with 3' UTR length.
- uORF number shows a weak correlation with 5' UTR length.
- Human genes with CPuORFs exhibit more MREs and lower evolutionary rates.
Conclusions:
- Species complexity influences 3' UTR evolution, impacting miRNA-mediated translational regulation.
- Conserved uORFs may be linked to enhanced miRNA responsiveness and slower evolution in genes.
- These findings offer novel insights into the interplay between UTR elements and translational control in animals.
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