Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells
| Autor: | Igor Ulitsky, Amira D. Mahmoud, Iraide Alloza, Julie Rodor, Margaret D. Ballantyne, Koen Vandenbroeck, Andrew H. Baker, Matthew R. Bennett, Vladislav Miscianinov |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Transcription Genetic Myocytes Smooth Muscle Datasets as Topic Computational biology 030204 cardiovascular system & hematology Biology Article Muscle Smooth Vascular Catalysis Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences long non-coding RNAs 0302 clinical medicine Transcription (biology) Gene expression Humans vascular smooth muscle cells RNA-Seq Physical and Theoretical Chemistry Enhancer Molecular Biology Gene lcsh:QH301-705.5 Aorta Spectroscopy Gene Expression Profiling Repertoire Organic Chemistry RNA RNA sequencing General Medicine Coronary Vessels Phenotype Plaque Atherosclerotic Computer Science Applications Enhancer Elements Genetic 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 cardiovascular system Cytokines Intercellular Signaling Peptides and Proteins RNA Long Noncoding enhancers Stress Mechanical Transcriptome |
| Zdroj: | Addi. Archivo Digital para la Docencia y la Investigación Universidad de Cantabria (UC) Addi: Archivo Digital para la Docencia y la Investigación Universidad del País Vasco International Journal of Molecular Sciences, Vol 22, Iss 1484, p 1484 (2021) Bennett, M, Ulitsky, I, Alloza, I, Vandenbroeck, K, Miscianinov, V, Mahmoud, A, Ballantyne, M, Rodor, J & Baker, A H 2021, ' Novel transcript discovery expands the repertoire of pathologically-associated, long non-coding RNAs in vascular smooth muscle cells ', International Journal of Molecular Sciences . https://doi.org/10.3390/ijms22031484 International Journal of Molecular Sciences Volume 22 Issue 3 instname |
| Popis: | 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. British Heart Foundation, European Research Council Advanced Grant VASCMIR and British/Israeli Collaborative grant BIRAX. |
| Databáze: | OpenAIRE |
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