PT - JOURNAL ARTICLE AU - Sekar, Vaishnovi AU - Mármol-Sánchez, Emilio AU - Kalogeropoulos, Panagiotis AU - Stanicek, Laura AU - Sagredo, Eduardo A. AU - Doukoumopoulos, Evangelos AU - Bonath, Franziska AU - Biryukova, Inna AU - Friedländer, Marc R. TI - agoTRIBE detects miRNA-target interactions transcriptome-wide in single cells AID - 10.1101/2022.08.10.503472 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.08.10.503472 4099 - http://biorxiv.org/content/early/2022/08/11/2022.08.10.503472.short 4100 - http://biorxiv.org/content/early/2022/08/11/2022.08.10.503472.full AB - MicroRNAs are gene regulatory molecules that play important roles in numerous biological processes including human health. The function of a given microRNA is defined by its selection of target transcripts, yet current state-of-the-art experimental methods to identify microRNA targets are laborious and require millions of cells. We have overcome these limitations by fusing the microRNA effector protein Argonaute2 to the RNA editing domain of ADAR2, allowing for the first time the detection of microRNA targets transcriptome-wide in single cells. Our agoTRIBE method reports functional microRNA targets which are additionally supported by evolutionary sequence conservation. As a proof-of-principle, we study microRNA interactions in single cells, and find substantial differential targeting across the cell cycle. Lastly, agoTRIBE additionally provides transcriptome-wide measurements of RNA abundance and will allow the deconvolution of microRNA targeting in complex samples such as tissues at the single-cell level.Competing Interest StatementThe authors have declared no competing interest.