title: Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway.
abstract: Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, we identify an LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. We show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, we demonstrate that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses and protecting cells against microbial infection.
authors.affiliation: a Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Wei Lun
authors.initials: WL
authors.lastname: Ng
authors.affiliation: b Department of Biology , Indiana University Bloomington , Bloomington , IL , USA.
authors.forename: Georgi K
authors.initials: GK
authors.lastname: Marinov
authors.affiliation: a Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Ee Shan
authors.initials: ES
authors.lastname: Liau
authors.affiliation: a Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Yi Lyn
authors.initials: YL
authors.lastname: Lam
authors.affiliation: a Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Yat-Yuen
authors.initials: YY
authors.lastname: Lim
authors.affiliation: a Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Chee-Kwee
authors.initials: CK
authors.lastname: Ea
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D021381:Protein Transport; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D020871:RNA Stability; D000079962:RNA, Circular; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D020663:ras Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012313:RNA; D000079962:RNA, Circular; D051197:Toll-Like Receptor 4; D020663:ras Guanine Nucleotide Exchange Factors; C543919:RASGEF1B protein, human
keywords: CircRNA; ICAM-1; LPS; RasGEF1B; TLR4