Selective RNA pseudouridinylation in situ by circular gRNAs in designer organelles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39448590.
- Also identified by DOI 10.1038/s41467-024-53403-1 and PMC identifier 11502668.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Pseudouridine
- Organelles
- RNA Editing
- RNA, Guide, CRISPR-Cas Systems
- RNA, Messenger