Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration

Vu Anh Truong, Yu-Han Chang, Thuc Quyen Dang, Yi Tu, Jui Tu, Chin-Wei Chang, Yi-Hao Chang, Guei-Sheung Liu and Yu-Chen Hu ()
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Vu Anh Truong: National Tsing Hua University
Yu-Han Chang: Chang Gung Memorial Hospital
Thuc Quyen Dang: National Tsing Hua University
Yi Tu: National Taiwan University
Jui Tu: National Taiwan University
Chin-Wei Chang: National Tsing Hua University
Yi-Hao Chang: National Tsing Hua University
Guei-Sheung Liu: Royal Victorian Eye and Ear Hospital
Yu-Chen Hu: National Tsing Hua University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Programmable RNA editing is harnessed for modifying mRNA. Besides mRNA, miRNA also regulates numerous biological activities, but current RNA editors have yet to be exploited for miRNA manipulation. To engineer primary miRNA (pri-miRNA), the miRNA precursor, we present a customizable editor REPRESS (RNA Editing of Pri-miRNA for Efficient Suppression of miRNA) and characterize critical parameters. The optimized REPRESS is distinct from other mRNA editing tools in design rationale, hence enabling editing of pri-miRNAs that are not editable by other RNA editing systems. We edit various pri-miRNAs in different cells including adipose-derived stem cells (ASCs), hence attenuating mature miRNA levels without disturbing host gene expression. We further develop an improved REPRESS (iREPRESS) that enhances and prolongs pri-miR-21 editing for at least 10 days, with minimal perturbation of transcriptome and miRNAome. iREPRESS reprograms ASCs differentiation, promotes in vitro cartilage formation and augments calvarial bone regeneration in rats, thus implicating its potentials for engineering miRNA and applications such as stem cell reprogramming and tissue regeneration.

Date: 2024
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DOI: 10.1038/s41467-024-52707-6

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