Do erythrocytic miRNA have a function?

Estell, Christopher (2018) Do erythrocytic miRNA have a function? PhD thesis, University of Glasgow.

Abstract

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.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QH Natural history > QH301 Biology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Copland, Prof. Mhairi
• Date of Award: 2018
• Depositing User: Mr Christopher Estell
• Unique ID: glathesis:2018-8899
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Mar 2018 09:20
• Last Modified: 19 Apr 2018 07:24
• URI: https://theses.gla.ac.uk/id/eprint/8899