title: Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor.
abstract: 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.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yehoshua
authors.identifier: http://orcid.org/0000-0001-6327-2845
authors.initials: Y
authors.lastname: Enuka
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Mattia
authors.initials: M
authors.lastname: Lauriola
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Morris E
authors.initials: ME
authors.lastname: Feldman
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Aldema
authors.initials: A
authors.lastname: Sas-Chen
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Igor
authors.initials: I
authors.lastname: Ulitsky
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel yosef.yarden@weizmann.ac.il.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
mesh_terms: D001940:Breast / Q000166:cytology; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics*; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics; D000079962:RNA, Circular; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000235:genetics
chemical_list: C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D035683:MicroRNAs; D000079962:RNA, Circular; D012333:RNA, Messenger; C587886:TGFA protein, human; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D012313:RNA