New characteristics of MiRNA and IsomiR interactions with mRNA

Studying the interactions between microRNAs/isomiRs and mRNAs is crucial due to their fundamental roles in gene regulation and disease. 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 reads, each pairing a microRNA or isomiR segment with an mRNA segment. We then identified 1747 isomiRs and over 5 million microRNA/isomiR-mRNA interactions from the complied data. We found that microRNAs with higher adenine and thymine content, and lower cytosine content, tend to have more isomiRs and target more mRNAs. Notably, 18.9% of mRNA targets were bound exclusively by isomiRs, not their microRNAs. Furthermore, isomiRs sharing the same seed sequences as their reference miRNAs may target different mRNAs from their miRNAs, suggesting functional divergence. Interestingly, 20.0% of microRNAs and 8.2% of isomiRs 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 region binding. Our findings provide new insights into the complexity of microRNA/isomiR-mRNA interactions.