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agoTRIBE detects miRNA-target interactions transcriptome-wide in single cells

Vaishnovi Sekar, Emilio Mármol-Sánchez, Panagiotis Kalogeropoulos, Laura Stanicek, Eduardo A. Sagredo, Evangelos Doukoumopoulos, Franziska Bonath, Inna Biryukova, View ORCID ProfileMarc R. Friedländer
doi: https://doi.org/10.1101/2022.08.10.503472
Vaishnovi Sekar
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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Emilio Mármol-Sánchez
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
3Centre for Palaeogenetics, Stockholm, Sweden
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Panagiotis Kalogeropoulos
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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Laura Stanicek
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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Eduardo A. Sagredo
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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Evangelos Doukoumopoulos
2Karolinska Institutet, Stockholm, Sweden
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Franziska Bonath
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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Inna Biryukova
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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  • For correspondence: inna.biryukova@scilifelab.se marc.friedlander@scilifelab.se
Marc R. Friedländer
1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden
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  • ORCID record for Marc R. Friedländer
  • For correspondence: inna.biryukova@scilifelab.se marc.friedlander@scilifelab.se
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 11, 2022.
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agoTRIBE detects miRNA-target interactions transcriptome-wide in single cells
Vaishnovi Sekar, Emilio Mármol-Sánchez, Panagiotis Kalogeropoulos, Laura Stanicek, Eduardo A. Sagredo, Evangelos Doukoumopoulos, Franziska Bonath, Inna Biryukova, Marc R. Friedländer
bioRxiv 2022.08.10.503472; doi: https://doi.org/10.1101/2022.08.10.503472
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agoTRIBE detects miRNA-target interactions transcriptome-wide in single cells
Vaishnovi Sekar, Emilio Mármol-Sánchez, Panagiotis Kalogeropoulos, Laura Stanicek, Eduardo A. Sagredo, Evangelos Doukoumopoulos, Franziska Bonath, Inna Biryukova, Marc R. Friedländer
bioRxiv 2022.08.10.503472; doi: https://doi.org/10.1101/2022.08.10.503472

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