Regulation of microRNAs and analysis of the splicing inhibitor Spliceostatin A
File(s)
Author(s)
Sarkar, Priti Rupa
Type
Thesis
Abstract
The advent of deep sequencing has revealed marked differences in microRNA
(miRNA) expression profiles between cell types. We focus on how miRNAs are
regulated in embryonic stem cells (ESCs) and their differentiated neural
progenitor stem cells (NPSCs). We discovered that 60% of miRNAs are regulated
b
y transcription. The remaining 40% of miRNAs were transcribed but not
processed in ESCs. Furthermore, systematic analysis of miRNAs on chromosome
1 and 2 helped to validate our results. We show that
43%
of these miRNAs,
which are highly expressed in differentiated cell types but poorly expressed in
ESCs, were transcribed but not processed in ESCs. Therefore we infer that post-
transcr
iptional regulation of miRNAs is prevalent in ESCs and could potentially
be a characteristic of this cell type.
Post-transcriptional regulation of miRNAs is also evident in miRNA clusters.
Clusters of miRNAs are transcribed together however individual mature miRNA
expression often differs between tissues and even within the same tissue type.
Following investigation into post-transcriptional regulation, we discovered
extensive alternative polyadenylation in three different miRNA clusters. We
suggest that alternative polyadenylation has the potential to influence regulation of individual miRNAs within a cluster contributing to their differential expression levels.
(miRNA) expression profiles between cell types. We focus on how miRNAs are
regulated in embryonic stem cells (ESCs) and their differentiated neural
progenitor stem cells (NPSCs). We discovered that 60% of miRNAs are regulated
b
y transcription. The remaining 40% of miRNAs were transcribed but not
processed in ESCs. Furthermore, systematic analysis of miRNAs on chromosome
1 and 2 helped to validate our results. We show that
43%
of these miRNAs,
which are highly expressed in differentiated cell types but poorly expressed in
ESCs, were transcribed but not processed in ESCs. Therefore we infer that post-
transcr
iptional regulation of miRNAs is prevalent in ESCs and could potentially
be a characteristic of this cell type.
Post-transcriptional regulation of miRNAs is also evident in miRNA clusters.
Clusters of miRNAs are transcribed together however individual mature miRNA
expression often differs between tissues and even within the same tissue type.
Following investigation into post-transcriptional regulation, we discovered
extensive alternative polyadenylation in three different miRNA clusters. We
suggest that alternative polyadenylation has the potential to influence regulation of individual miRNAs within a cluster contributing to their differential expression levels.
Version
Open Access
Date Issued
2013-05
Date Awarded
2013-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Dibb, Nick
Publisher Department
Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)