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circRAB3IP modulates cell proliferation by reorganizing gene expression and mRNA processing in a paracrine manner

Circular RNAs are an endogenous long-lived and abundant noncoding species. Despite their prevalence, only a few circRNAs have been dissected mechanistically to date. Here, we cataloged nascent RNA-enriched circRNAs from primary human cells and functionally assigned a role to circRAB3IP in sustaining...

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Main Authors: Josipovic, Natasa (Author) , Ebbesen, Karoline K. (Author) , Zirkel, Anne (Author) , Danieli-Mackay, Adi (Author) , Dieterich, Christoph (Author) , Kurian, Leo (Author) , Hansen, Thomas B. (Author) , Papantonis, Argyris (Author)
Format: Article (Journal)
Language:English
Published: August 16, 2022
In: RNA
Year: 2022, Volume: 28, Issue: 11, Pages: 1481-1495
ISSN:1469-9001
DOI:10.1261/rna.079195.122
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1261/rna.079195.122
Verlag, lizenzpflichtig, Volltext: https://rnajournal.cshlp.org/content/28/11/1481
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Author Notes:Natasa Josipovic, Karoline K. Ebbesen, Anne Zirkel, Adi Danieli-Mackay, Christoph Dieterich, Leo Kurian, Thomas B. Hansen and Argyris Papantonis
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Summary:Circular RNAs are an endogenous long-lived and abundant noncoding species. Despite their prevalence, only a few circRNAs have been dissected mechanistically to date. Here, we cataloged nascent RNA-enriched circRNAs from primary human cells and functionally assigned a role to circRAB3IP in sustaining cellular homeostasis. We combined "omics" and functional experiments to show how circRAB3IP depletion deregulates hundreds of genes, suppresses cell cycle progression, and induces senescence-associated gene expression changes. Conversely, excess circRAB3IP delivered to endothelial cells via extracellular vesicles suffices for accelerating their division. We attribute these effects to an interplay between circRAB3IP and the general splicing factor SF3B1, which can affect transcript variant expression levels of cell cycle-related genes. Together, our findings link the maintenance of cell homeostasis to the presence of a single circRNA.
Item Description:Gesehen am 24.10.2023
Physical Description:Online Resource
ISSN:1469-9001
DOI:10.1261/rna.079195.122

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