Ana Quiles-Jiménez1, Ida Gregersen1, Mirta Mittelstedt Leal de Sousa2, Azhar Abbas3, Xiang Yi Kong4, Ingrun Alseth5, Sverre Holm4, Tuva B Dahl4, Karolina Skagen6, Mona Skjelland6, Pål Aukrust7, Magnar Bjørås2, Bente Halvorsen8. 1. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Faculty of Medicine, University of Oslo, Norway. 2. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; PROMEC Core Facility for Proteomics and Metabolomics, NTNU and the Central Norway Regional Health Authority, Trondheim, Norway. 3. Department of Neurology, Østfold Hospital Trust Kalnes, Grålum, Norway. 4. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway. 5. Department of Microbiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 6. Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 7. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Norway. 8. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Faculty of Medicine, University of Oslo, Norway. Electronic address: Bente.Halvorsen@rr-research.no.
Abstract
BACKGROUND: More than 170 post-transcriptional RNA modifications regulate the localization, processing and function of cellular RNAs, and aberrant RNA modifications have been linked to a range of human diseases. The RNA modification landscape in atherosclerosis, the main underlying cause of cardiovascular diseases, is still largely unknown. METHODS: We used mass spectrometry to analyse a selection of RNA-modifying enzymes and the N6-methyladenosine (m6A) in carotid atherosclerotic lesion samples representing early and advanced stages of atherosclerosis as compared to non-atherosclerotic arteries from healthy controls. FINDINGS: (i) the detection of different levels of several enzymes involved in methylations occurring in rRNA and mRNA; (ii) these findings included changes in the levels of methyltransferases ('writers'), binding proteins ('readers') and demethylases ('erasers') during atherosclerosis as compared to non-atherosclerotic control arteries, with generally the most prominent differences in samples from early atherosclerotic lesions; and (iii) these changes were accompanied by a marked downregulation of m6A in rRNA, the most abundant and well-studied modification in mRNA with a wide range of effects on cell biology. INTERPRETATION: We show for the first time that RNA-modifying enzymes and the well-studied RNA modification m6A are differentially regulated in atherosclerotic lesions, which potentially could help creating new prognostic and treatment strategies.
BACKGROUND: More than 170 post-transcriptional RNA modifications regulate the localization, processing and function of cellular RNAs, and aberrant RNA modifications have been linked to a range of human diseases. The RNA modification landscape in atherosclerosis, the main underlying cause of cardiovascular diseases, is still largely unknown. METHODS: We used mass spectrometry to analyse a selection of RNA-modifying enzymes and the N6-methyladenosine (m6A) in carotid atherosclerotic lesion samples representing early and advanced stages of atherosclerosis as compared to non-atherosclerotic arteries from healthy controls. FINDINGS: (i) the detection of different levels of several enzymes involved in methylations occurring in rRNA and mRNA; (ii) these findings included changes in the levels of methyltransferases ('writers'), binding proteins ('readers') and demethylases ('erasers') during atherosclerosis as compared to non-atherosclerotic control arteries, with generally the most prominent differences in samples from early atherosclerotic lesions; and (iii) these changes were accompanied by a marked downregulation of m6A in rRNA, the most abundant and well-studied modification in mRNA with a wide range of effects on cell biology. INTERPRETATION: We show for the first time that RNA-modifying enzymes and the well-studied RNA modification m6A are differentially regulated in atherosclerotic lesions, which potentially could help creating new prognostic and treatment strategies.
Authors: Daphne A L van den Homberg; Reginald V C T van der Kwast; Paul H A Quax; A Yaël Nossent Journal: Int J Mol Sci Date: 2022-01-19 Impact factor: 5.923