Selective RNA pseudouridinylation in situ by circular gRNAs in designer organelles

RNA modifications play a pivotal role in the regulation of RNA chemistry within cells. Several technologies have been developed with the goal of using RNA modifications to regulate cellular biochemistry selectively, but achieving selective and precise modifications remains a challenge. Here, we show that by using designer organelles, we can modify mRNA with pseudouridine in a highly selective and guide-RNA-dependent manner. We use designer organelles inspired by concepts of phase separation, a central tenet in developing artificial membraneless organelles in living mammalian cells. In addition, we use circular guide RNAs to markedly enhance the effectiveness of targeted pseudouridinylation. Our studies introduce spatial engineering through optimized RNA editing organelles (OREO) as a complementary tool for targeted RNA modification, providing new avenues to enhance RNA modification specificity.

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Publication Details

Journal
Nature Communications
Published
2024-10-24
DOI
https://doi.org/10.1038/s41467-024-53403-1
Citations
9
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
2.10

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article

Selective RNA pseudouridinylation in situ by circular gRNAs in designer organelles

Mark Helm, Susanne Gerber, Cosimo Jann, Stefan Mündnich et al.
9 citations
Nature Communications
RNA modifications and cancer
2.10
article

Selective RNA pseudouridinylation in situ by circular gRNAs in designer organelles

Mark Helm, Susanne Gerber, Cosimo Jann, Stefan Mündnich, Edward A. Lemke, Virginie Marchand, Anna Wierczeiko, Lukas Schartel, Tamer Butto, Yuri Motorin
article en
9 citations

Abstract

RNA modifications play a pivotal role in the regulation of RNA chemistry within cells. Several technologies have been developed with the goal of using RNA modifications to regulate cellular biochemistry selectively, but achieving selective and precise modifications remains a challenge. Here, we show that by using designer organelles, we can modify mRNA with pseudouridine in a highly selective and guide-RNA-dependent manner. We use designer organelles inspired by concepts of phase separation, a central tenet in developing artificial membraneless organelles in living mammalian cells. In addition, we use circular guide RNAs to markedly enhance the effectiveness of targeted pseudouridinylation. Our studies introduce spatial engineering through optimized RNA editing organelles (OREO) as a complementary tool for targeted RNA modification, providing new avenues to enhance RNA modification specificity.

Nature CommunicationsVol. 15(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Johannes Gutenberg University Mainz (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Institute of Biophysics and Cell Engineering (BY), Ingénierie Moléculaire et Physiopathologie Articulaire (FR), Institute of Molecular Biology (DE), Université de Lorraine (FR)
Deutsche Forschungsgemeinschaft
Openalex Percentile: Top 12%
RNA modifications and cancer
2.10
DOIOpen Access PDFOpenAlex
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