Novel features of miRNA and isomiR-mRNA interactions

2025 · doi:10.1101/2025.05.12.653582
preprint OA: closed CC-BY-NC-ND-4.0
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This study identified 1,747 human isomiRs and over 5 million interactions, revealing that A/T-rich miRNAs have more isomiRs and targets, with isomiRs exclusively targeting some mRNAs and both isomiRs and miRNAs binding independently of seed regions.

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The paper analyzes human chimeric sequencing reads to characterize microRNA and isomiR pairing with mRNA fragments, compiling 1,747 isomiRs and over 5 million miRNA/isomiR–mRNA interactions. It reports that microRNAs with higher adenine/thymine and lower cytosine content show more isomiRs and more mRNA targets, and that an average of 18.9% of mRNA targets are bound exclusively by isomiRs rather than by their reference microRNAs. It also finds that seed-sharing isomiRs can bind different targets than their parent microRNAs, and that a subset of microRNAs (20.0%) and isomiRs (8.2%) bind independently of seed regions, with most seed-using species also involving non-seed regions. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Studying the interactions between microRNAs/isomiRs and mRNAs is critical due to their fundamental roles in gene regulation and their involvement in various diseases. Although many isomiRs have been identified, the analysis of their interactions with mRNAs remains in its early stages. In this study, we compiled available human chimeric read data, each comprising a microRNA or isomiR segment paired with an mRNA fragment and identified 1,747 isomiRs and over 5 million microRNA/isomiR–mRNA interactions. We observed that microRNAs with higher adenine and thymine content, and lower cytosine content, tend to have more isomiRs and more mRNA targets. Notably, an average of 18.9% of mRNA targets were bound exclusively by isomiRs, not by their microRNA counterparts. Furthermore, isomiRs sharing the same seed sequences as their reference microRNAs may bind to different targets from their microRNAs, highlighting functional divergence. Interestingly, 20.0% of microRNAs and 8.2% of isomiRs appear to bind mRNAs independently of their seed regions. Among those that do utilize seed regions, 94.5% of microRNAs and 95.7% of isomiRs also engage non-seed regions, suggesting a broader and more complex binding behavior. Our findings offer new insights into microRNA/isomiR–mRNA interactions.
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Abstract Studying the interactions between microRNAs/isomiRs and mRNAs is critical due to their fundamental roles in gene regulation and their involvement in various diseases. Although many isomiRs have been identified, the analysis of their interactions with mRNAs remains in its early stages. In this study, we compiled available human chimeric read data, each comprising a microRNA or isomiR segment paired with an mRNA fragment and identified 1,747 isomiRs and over 5 million microRNA/isomiR–mRNA interactions. We observed that microRNAs with higher adenine and thymine content, and lower cytosine content, tend to have more isomiRs and more mRNA targets. Notably, an average of 18.9% of mRNA targets were bound exclusively by isomiRs, not by their microRNA counterparts. Furthermore, isomiRs sharing the same seed sequences as their reference microRNAs may bind to different targets from their microRNAs, highlighting functional divergence. Interestingly, 20.0% of microRNAs and 8.2% of isomiRs appear to bind mRNAs independently of their seed regions. Among those that do utilize seed regions, 94.5% of microRNAs and 95.7% of isomiRs also engage non-seed regions, suggesting a broader and more complex binding behavior. Our findings offer new insights into microRNA/isomiR–mRNA interactions. Competing Interest Statement The authors have declared no competing interest.

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License: CC-BY-NC-ND-4.0