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bioRxiv · 10.1101/2024.05.28.596158

Competition effects regulating the composition of the microRNA pool

Raak, S. B.·Hanley, J. G.·O'Donnell, C.
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Abstract

MicroRNAS (miRNAs) are short non-coding RNAs that can repress mRNA translation to regulate protein synthesis. During their maturation, multiple types of pre-miRNAs compete for a shared pool of the enzyme Dicer. It is unknown how this competition for a shared resource influences the relative expression of mature miRNAs. We study this process in a computational model of pre-miRNA maturation, fitted to in vitro Drosophila S2 cell data. We find that those pre-miRNAs which efficiently interact with Dicer outcompete other pre-miRNAs, when Dicer is scarce. To test our model predictions, we re-analysed previously published ex vivo mouse striatum data with reduced Dicer1 expression. We calculated a proxy measure for pre-miRNA affinity to TRBP (a protein which loads pre-miRNAs to Dicer). This measure well-predicted mature miRNA levels in the data, validating our assumptions. We used this as a basis to test the the models predictions through further analysis of the data. We found that pre-miRNAs with strong TRBP association are over-represented in competition conditions, consistent with the modelling. Finally using further simulations, we discovered that pre-miRNAs with low maturation rates can affect the mature miRNA pool via competition among pre-miRNAs. Overall, this work presents evidence of pre-miRNA competition regulating the composition of mature miRNAs.

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Raak, S. B., Hanley, J. G., O'Donnell, C.. 2024-05-29. Competition effects regulating the composition of the microRNA pool. https://doi.org/10.1101/2024.05.28.596158

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