GEO series

Cytoplasmic DIS3 degrades circular RNAs independently of the exosome

GSE261223 Homo sapiens Expression profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing 4 samples Submitted 2025/12/21 Platform GPL24676

Summary

Circular RNAs (circRNAs) are frequently generated during splicing. Their physiological roles, however, remain largely elusive. Some specific circRNAs function as microRNA (miRNA) or RNA binding protein (RBP) sponges or encode for proteins and are actively translated. Due to the lack of accessible ends, circRNAs are resistant to exonucleolytic cleavage and thus are more stable than linear RNAs. Nevertheless, circRNAs are most likely turned over by cellular degradation pathways. Here, we used a biochemical purification strategy to find nucleases that could degrade circRNAs. We identified the exosome-associated nuclease DIS3, which contains an endonucleolytic PIN domain and an exonuclease domain. We show that DIS3 can degrade circRNAs independently of the exosome in vitro. Although moderately, RNA-seq reveals that selected circRNAs are stabilized when DIS3 is reduced in vivo. Based on our data, we propose a model, in which cytoplasmic DIS3 contributes to the turnover of circRNAs in human cells.

Published in

Cytoplasmic DIS3 is an exosome-independent endoribonuclease with catalytic activity toward circular RNAs

Latini C, Eichlinger J, Fuchs AL et al. · Cell reports 2025 · PMID 40440169 · doi:10.1016/j.celrep.2025.115769

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Also filed as BioProject PRJNA1085775 and SRA study SRP494222. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40440169) ↗

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