miRNA regulation in brain tissue space: the 3′UTR perspective
- Denise Aigner1,2,10,
- Florian Bartsch1,2,3,10,
- Poojashree Bhaskar1,2,10,
- Lisa Emmenegger1,2,10,
- Nikos Karaiskos1,
- Nikolaus Rajewsky1,4,5,6,7,8 and
- Agnieszka Rybak-Wolf9
- 1Laboratory for Systems Biology of Regulatory Elements, Berlin Institute for Medical Systems Biology (BIMSB), Max-Delbrück-Centrum for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany
- 2Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- 3Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
- 4Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
- 5German Center for Cardiovascular Research (DZHK), 10785 Berlin, Germany
- 6NeuroCure Cluster of Excellence, 10117 Berlin, Germany
- 7German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
- 8National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- 9Organoid Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany
- Corresponding author: rajewsky{at}mdc-berlin.de
-
↵10 These authors contributed equally to this work.
Abstract
MicroRNAs (miRNAs) are key regulators of gene expression in both health and disease. Their expression and regulatory functions are highly complex and spatiotemporally organized within tissues. In recent years, spatial transcriptomics has made significant progress in quantifying RNA expression at subcellular resolution in tissue sections. However, no current method can quantify miRNAs and their target 3′ untranslated regions (3′UTRs) in space simultaneously. Furthermore, although 3′UTRs harbor critical miRNA target sites, 3′UTR isoform variation in space is largely unexplored. In this review, we discuss the role of miRNA-mediated regulation. We focus on neurodevelopment and neuronal function, where miRNAs and 3′UTRs have particularly complex and important functions. We summarize current experimental and computational approaches for spatial quantification of miRNAs and 3′UTRs, highlight existing challenges, and propose strategies for future research.
Keywords
This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
