Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins

Connerty, Patrick Peter

Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins

Connerty, Patrick Peter

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Publication Type:: Thesis
Issue Date:: 2016

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Field	Value	Language
dc.contributor.author	Connerty, Patrick Peter
dc.date.accessioned	2017-04-05T03:38:11Z
dc.date.available	2017-04-05T03:38:11Z
dc.date.issued	2016
dc.identifier.uri	http://hdl.handle.net/10453/90062
dc.description	University of Technology Sydney. Faculty of Science.	en_AU
dc.description.abstract	microRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate gene expression. As miRNAs control many important biological processes it is important that their own production is highly controlled too. A range of auxiliary proteins involved in regulating miRNA biogenesis have been documented extensively, highlighting the complexity of the miRNA pathway. This study identifies novel roles of RNA binding proteins which are both canonical and auxiliary to the miRNA biogenesis pathway. Here, we demonstrate that inhibition of p72 and KHSRP decreases Ago2 protein stability through disturbing miRNA biogenesis and therefore miRNA abundance. Furthermore, we have demonstrated that Ago2 is subject to multiple types of regulation as transient knockdown of Dicer stabilises Ago2 protein despite a decrease in miRNA abundance via an unknown mechanism. Additionally, we have established that miRNA biogenesis is subject to a possible negative feedback mechanisms in which impairment of Dicer function both promotes and inhibits pri-miRNA production in a pri-miRNA and cell specific manner. Finally, this study provides evidence to suggest that both mature miRNA levels and miRNA target abundance can stabilise miRNA biogenesis and promote pri-miRNA production in the absence of key and auxiliary proteins involved in miRNA biogenesis.	en_AU
dc.format	Thesis (PhD)
dc.language.iso	en_AU	en_AU
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/90062/7/02whole.pdf
dc.rights	au.edu.uts.lib/ppc
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	microRNAs (miRNAs)	en
dc.subject	miRNA biogenesis.	en
dc.subject	RNA binding proteins.	en
dc.subject	p72 and KHSRP.	en
dc.subject	Ago2 protein stability.	en
dc.subject	Dicer.	en
dc.subject	pri-miRNA.	en
dc.title	Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins	en_AU
dc.type	Thesis	en_AU
utslib.copyright.status	open_access

Abstract:

microRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate gene expression. As miRNAs control many important biological processes it is important that their own production is highly controlled too. A range of auxiliary proteins involved in regulating miRNA biogenesis have been documented extensively, highlighting the complexity of the miRNA pathway. This study identifies novel roles of RNA binding proteins which are both canonical and auxiliary to the miRNA biogenesis pathway. Here, we demonstrate that inhibition of p72 and KHSRP decreases Ago2 protein stability through disturbing miRNA biogenesis and therefore miRNA abundance. Furthermore, we have demonstrated that Ago2 is subject to multiple types of regulation as transient knockdown of Dicer stabilises Ago2 protein despite a decrease in miRNA abundance via an unknown mechanism. Additionally, we have established that miRNA biogenesis is subject to a possible negative feedback mechanisms in which impairment of Dicer function both promotes and inhibits pri-miRNA production in a pri-miRNA and cell specific manner. Finally, this study provides evidence to suggest that both mature miRNA levels and miRNA target abundance can stabilise miRNA biogenesis and promote pri-miRNA production in the absence of key and auxiliary proteins involved in miRNA biogenesis.

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http://hdl.handle.net/10453/90062