Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor

By Yehoshua Enuka, M. Lauriola, M. Feldman, A. Sas-Chen, Igor Ulitsky, Y. Yarden. Nucleic Acids Research, 2015

650 citations recorded by the source corpus.

Circular RNAs (circRNAs) are widespread circles of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and microRNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms with no detectable circRNAs. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9a434cfe03679e43c3908f535ee1c9257b951114

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Ling-Ling Chen
2. Li Yang
3. Stas Wüst
4. Sebastian Kadener
5. I. Patop

In Molecular Biology

1. Ling-Ling Chen
2. Li Yang
3. Sebastian Kadener
4. Stas Wüst
5. I. Patop

Citations in the corpus

• Circular RNAs: Promising Biomarkers for Human Diseases (2018, background): “[1] Stability: due to the covalently closed loop structure lacking of free 5′ and 3′ ends, circRNA molecules are highly resistant to exonuclease RNase R, which makes themmuchmore stable compared to linear RNAs [6,34].”
• The bioinformatics toolbox for circRNA discovery and analysis (2020, background): “CircRNAs also were shown to be long-lived [32].”
• Past, present, and future of circRNAs (2019, positive): “An in vitro study of 60 circRNAs in cell culture using 4-thiouridine metabolic labeling demonstrated that most of the assayed circRNAs have longer half-lives (18.8 – 23.7 h) than their linear counterparts (4.0 – 7.4 h; Enuka et al , 2016).”
• Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity. (2019, positive): “circRNAs Are Significantly Downregulated in Cells upon Poly(I:C) Treatment or Viral Infection As circRNAs are stable in examined cells and tissues under normal conditions (Enuka et al., 2016; Zhang et al., 2016b), we”