Despite being translationally null, erythrocytes contain miRNA at concentrations equal to nucleated cells, meaning that of the miRNA found in peripheral blood ~ 99 % is located in red cells. Despite this huge abundance, the literature currently regards erythrocytic miRNA (e-miRNA) as redundant. Data from Hamilton lab challenges this notion as it shows that e-miRNA are stable, maintain a catalytic potential, and have sequence profiles similar across species, indicating conservation. This thesis investigates what the potential function of emiRNA could be, both within erythrocytes and in other cells. To develop hypotheses, RISC-protein interactions were evaluated unearthing the appearance of an apparently post-translationally modified AGO2; what this modification is, remains to be defined. As part of a homeostatic hypothesis, the idea that e-miRNA may act as a molecular signal and regulate the transcriptome of phagocytosing cells was evaluated. However, it was discovered that e-miRNA are lost as RBCs age, potentially through vesicularisation. The differences between RBC vesicles that occur in vivo and those that occur when blood is stored ready for transfusion were evaluated. This highlighted a potential artefact within the literature with regards to what is termed as “microvesicles” (MVs). The clinical concern regarding storage MVs was evaluated through the generation of a phago/endocytosis model, and consistent with recent publications, no mal-effect was observed. This portion of the study highlighted a secondary structure within macrophages that is not a phagolysosome, but does process internalised RBC-MVs.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:739258 |
| Date | January 2018 |
| Creators | Estell, Christopher |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/8899/ |
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