Endothelial function and dysfunction in the cardiovascular system: the long non-coding road

Figure 1. LncRNA classification and function. LncRNAs can be categorized based on their transcription start site, surrounding coding genes and regulatory function. Promoter-derived transcripts are more likely to be spliced, poly-adenylated, lengthy and stable when compared with enhancer-derived which, though separately categorized as eRNAs, are often included in lncRNA studies if >200 bp. The position of a lncRNA relative to surrounding coding genes as a categorization method provides indication of potential lncRNA function, e.g. bidirectional transcripts likely impact their partner gene. LncRNAs whose function has been characterized fall into distinct groups based on the its molecular interactions and the mechanism of action used to impact gene transcription or translation. As components of RNP complexes, lncRNAs can regulate the activity or localization of a particular protein, or play a structural role within a larger protein complex. LncRNAs can also control gene transcription by modulating the activity of transcription factors, or through the recruitment of chromatin modifying complexes. In addition to acting as miRNA host genes, lncRNAs can function as miRNA sponges, titrating…

Figure 2. Known function of endothelial lncRNAs. List of lncRNAs reported to have endothelial regulatory functions with impact on cell differentiation, EndMT, angiogenesis, inflammation, EHT, and vessel homeostasis. EHT, endothelial-to-haematopoietic transition; EndMT, endothelial-to-mesenchymal transition.

Figure 3. Considerations for lncRNA discovery. Common concepts to consider at the design stage for studies identifying lncRNA within sequencing data. These are generally tailored depending on the aims of the study, for instance it is often not necessary to profile for previously unannotated lncRNAs across the whole transcriptome to find candidates of interest though studies with such scope can have greater power.

Figure 4. RNA-focused pulldown strategies. Workflow for the identification of lncRNA interactions using exogenous (left) or endogenous RNA pull-down strategies.