MicroRNAs (miRNAs) are small regulatory RNAs that destabilize partially complementary transcripts and cleave perfectly paired targets. miRNAs are often expressed in a specific tissue, allowing miRNA-directed cleavage to be used to prevent genome editing or gene replacement therapy in unintended cell types, a strategy called detargeting. miRNA intracellular concentration influences the potency of gene silencing, yet the absolute steady-state levels of just a few miRNAs have been determined in mammalian tissues. Here, we report the absolute abundance of miRNAs in 14 human and mouse cell lines and 17 mouse tissues, including eight brain regions. Our experiments in human cultured cells demonstrate that both miRNA and target levels influence efficacy of cleavage of fully complementary transcripts. We report the miRNA concentration required for productive cleavage of highly expressed transcripts and identify mouse miRNAs that reach this threshold in vivo.
Keywords: absolute abundance; detargeting; microRNA; tissue-specific expression.
© 2025 Kraus et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.