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Article

Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells

1
Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
2
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
3
Inflammation & Biomarkers Group, Biocruces Bizkaia Health Research Institute, Cruces Plaza, 48903 Barakaldo, Spain
4
Ikerbasque, Basque Foundation for Science, 3 María Díaz Haroko Kalea, 48013 Bilbao, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Miguel Hueso and Estanislao Navarro
Int. J. Mol. Sci. 2021, 22(3), 1484; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031484
Received: 13 January 2021 / Revised: 28 January 2021 / Accepted: 29 January 2021 / Published: 2 February 2021
(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)
Vascular smooth muscle cells (VSMCs) provide vital contractile force within blood vessel walls, yet can also propagate cardiovascular pathologies through proliferative and pro-inflammatory activities. Such phenotypes are driven, in part, by the diverse effects of long non-coding RNAs (lncRNAs) on gene expression. However, lncRNA characterisation in VSMCs in pathological states is hampered by incomplete lncRNA representation in reference annotation. We aimed to improve lncRNA representation in such contexts by assembling non-reference transcripts in RNA sequencing datasets describing VSMCs stimulated in vitro with cytokines, growth factors, or mechanical stress, as well as those isolated from atherosclerotic plaques. All transcripts were then subjected to a rigorous lncRNA prediction pipeline. We substantially improved coverage of lncRNAs responding to pro-mitogenic stimuli, with non-reference lncRNAs contributing 21–32% for each dataset. We also demonstrate non-reference lncRNAs were biased towards enriched expression within VSMCs, and transcription from enhancer sites, suggesting particular relevance to VSMC processes, and the regulation of neighbouring protein-coding genes. Both VSMC-enriched and enhancer-transcribed lncRNAs were large components of lncRNAs responding to pathological stimuli, yet without novel transcript discovery 33–46% of these lncRNAs would remain hidden. Our comprehensive VSMC lncRNA repertoire allows proper prioritisation of candidates for characterisation and exemplifies a strategy to broaden our knowledge of lncRNA across a range of disease states. View Full-Text
Keywords: vascular smooth muscle cells; long non-coding RNAs; RNA sequencing; enhancers vascular smooth muscle cells; long non-coding RNAs; RNA sequencing; enhancers
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MDPI and ACS Style

Bennett, M.; Ulitsky, I.; Alloza, I.; Vandenbroeck, K.; Miscianinov, V.; Mahmoud, A.D.; Ballantyne, M.; Rodor, J.; Baker, A.H. Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells. Int. J. Mol. Sci. 2021, 22, 1484. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031484

AMA Style

Bennett M, Ulitsky I, Alloza I, Vandenbroeck K, Miscianinov V, Mahmoud AD, Ballantyne M, Rodor J, Baker AH. Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells. International Journal of Molecular Sciences. 2021; 22(3):1484. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031484

Chicago/Turabian Style

Bennett, Matthew, Igor Ulitsky, Iraide Alloza, Koen Vandenbroeck, Vladislav Miscianinov, Amira D. Mahmoud, Margaret Ballantyne, Julie Rodor, and Andrew H. Baker. 2021. "Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells" International Journal of Molecular Sciences 22, no. 3: 1484. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031484

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