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Assessing the functional association of intronic miRNAs with their host genes
Avital Steiman-Shimony1, Orr Shtrikman1, Hanah Margalit1
1Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Abstract:
In human, nearly half of the known microRNAs (miRNAs) are encoded within the introns of protein-coding genes. The embedment of these miRNA genes within the sequences of protein-coding genes alludes to a possible functional relationship between intronic miRNAs and their hosting genes. Several studies, using predicted targets, suggested that intronic miRNAs influence their hosts' function either antagonistically or synergistically. New experimental data of miRNA expression patterns and targets enable exploring this putative association by relying on actual data rather than on predictions. Here, our analysis based on currently available experimental data implies that the potential functional association between intronic miRNAs and their hosting genes is limited. For host-miRNA examples where functional associations were detected, it was manifested by either autoregulation, common targets of the miRNA and hosting gene, or through the targeting of transcripts participating in pathways in which the host gene is involved. This low prevalence of functional association is consistent with our observation that many intronic miRNAs have independent transcription start sites and are not coexpressed with the hosting gene. Yet, the intronic miRNAs that do show functional association with their hosts were found to be more evolutionarily conserved compared to other intronic miRNAs. This might suggest a selective pressure to maintain this architecture when it has a functional consequence.
Insights
Most microRNAs (miRNAs) encoded in introns show limited functional links with their host genes. However, conserved intronic miRNAs with functional associations suggest selective pressure for this gene architecture.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Nearly half of human microRNAs (miRNAs) are encoded within introns of protein-coding genes.
- The proximity suggests potential functional relationships between intronic miRNAs and their host genes.
- Previous studies, relying on predicted targets, indicated possible synergistic or antagonistic roles.
Purpose of the Study:
- To investigate the functional association between intronic miRNAs and their hosting genes using experimental data.
- To determine the prevalence and mechanisms of functional interactions between host genes and intronic miRNAs.
- To explore the evolutionary conservation of intronic miRNAs with functional associations.
Main Methods:
- Analysis of current experimental data on miRNA expression patterns and validated targets.
- Examination of host-miRNA examples for autoregulation, common targets, and pathway involvement.
- Comparison of evolutionary conservation between intronic miRNAs with and without functional associations.
Main Results:
- The analysis indicates a limited functional association between most intronic miRNAs and their hosting genes.
- Detected functional associations involve autoregulation, shared targets, or targeting of related pathways.
- Intronic miRNAs showing functional links with hosts are more evolutionarily conserved than others.
- Many intronic miRNAs exhibit independent transcription and lack coexpression with host genes.
Conclusions:
- The functional interplay between intronic miRNAs and host genes is less prevalent than previously assumed.
- Functional associations, when present, are maintained through specific mechanisms and show higher evolutionary conservation.
- The findings suggest selective pressure to preserve the intronic miRNA-host gene architecture when it confers functional advantages.
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