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Characterization of protein isoform diversity in human umbilical vein endothelial cells via long-read proteogenomics.
Mehlferber, Madison M; Jeffery, Erin D; Saquing, Jamie; Jordan, Ben T; Sheynkman, Leon; Murali, Mayank; Genet, Gael; Acharya, Bipul R; Hirschi, Karen K; Sheynkman, Gloria M.
Afiliación
  • Mehlferber MM; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
  • Jeffery ED; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
  • Saquing J; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
  • Jordan BT; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
  • Sheynkman L; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
  • Murali M; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
  • Genet G; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
  • Acharya BR; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Hirschi KK; Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Sheynkman GM; Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
RNA Biol ; 19(1): 1228-1243, 2022 01.
Article en En | MEDLINE | ID: mdl-36457147
Endothelial cells (ECs) comprise the lumenal lining of all blood vessels and are critical for the functioning of the cardiovascular system. Their phenotypes can be modulated by alternative splicing of RNA to produce distinct protein isoforms. To characterize the RNA and protein isoform landscape within ECs, we applied a long read proteogenomics approach to analyse human umbilical vein endothelial cells (HUVECs). Transcripts delineated from PacBio sequencing serve as the basis for a sample-specific protein database used for downstream mass-spectrometry (MS) analysis to infer protein isoform expression. We detected 53,863 transcript isoforms from 10,426 genes, with 22,195 of those transcripts being novel. Furthermore, the predominant isoform in HUVECs does not correspond with the accepted "reference isoform" 25% of the time, with vascular pathway-related genes among this group. We found 2,597 protein isoforms supported through unique peptides, with an additional 2,280 isoforms nominated upon incorporation of long-read transcript evidence. We characterized a novel alternative acceptor for endothelial-related gene CDH5, suggesting potential changes in its associated signalling pathways. Finally, we identified novel protein isoforms arising from a diversity of RNA splicing mechanisms supported by uniquely mapped novel peptides. Our results represent a high-resolution atlas of known and novel isoforms of potential relevance to endothelial phenotypes and function.[Figure: see text].
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteogenómica Límite: Humans Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteogenómica Límite: Humans Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos