miRNAmiRNA

miRNAmiRNA refers to regulatory interactions between microRNAs themselves, extending beyond the canonical role of miRNAs as silencers of messenger RNAs. The term describes how different miRNAs can influence each other’s expression, maturation, stability, or activity within complex gene regulatory networks. While miRNAs primarily repress target transcripts, miRNAmiRNA interactions can shape the global output of post-transcriptional regulation by modulating miRNA abundance and function.

Evidence for miRNAmiRNA interactions includes indirect effects through shared targets that encode components of the miRNA biogenesis machinery, feedback circuits where miRNAs regulate transcription factors controlling other miRNA genes, and competition among miRNAs at overlapping target sites generating ceRNA-like influences. Some studies report direct miRNA–miRNA contacts detected by crosslinking-and-immunoprecipitation approaches, but such interactions are controversial and require extensive validation; direct binding between mature miRNAs remains a topic of active investigation.

In development and disease, miRNAmiRNA networks can fine-tune gene repression by altering the availability and activity of miRNA families. Changes in these interactions may affect pathways governing cell fate, proliferation, stress responses, and metabolism. Because the networks are highly context dependent, the biological relevance of individual miRNA–miRNA interactions often varies by tissue, developmental stage, and species.

Research approaches combine high-throughput sequencing with crosslinking, miRNA–RNA interaction mapping, network inference, and perturbation experiments to infer and validate miRNA–miRNA links. Distinguishing direct miRNA–miRNA contacts from indirect effects remains challenging. As data accumulate, the concept of miRNAmiRNA is increasingly used to describe an emerging layer of post-transcriptional regulation, with potential implications for understanding regulatory robustness and disease mechanisms.