Regulation of exogenous retroviruses and endogenous retroelements by MOV10

Retroelements are some of the most successful parasites studied because of their ability to reverse transcribe and permanently integrate into the host genome. Host cells have, therefore, evolved multiple control mechanisms, such as cellular restriction factors, to protect their genomes from the pathogenic and mutagenic effects of retroelements. Identification of the full complement of these proteins is vital to comprehend the capacity of the host to regulate these genetic parasites. Human MOV10 is a putative RNA helicase with inhibitory or stimulatory roles in the replication of several RNA viruses, and the homologs of which play vital roles in the restriction of viruses and endogenous retroelements. Furthermore, MOV10 interacts with antiviral APOBEC3 proteins and core post-transcriptional RNA silencing machinery, all of which colocalise in cytoplasmic mRNA processing bodies and stress granules. Considering MOV10 cellular associations and homolog functions, the capacity of MOV10 to regulate the replication of a diverse panel of genetically distinct retroelements was investigated here.<br/>Ectopically overexpressed MOV10 potently restricts the replication of retroviruses as well as the propagation of LTR and non-LTR endogenous retroelements. Significantly,RNAi-mediated silencing of endogenous MOV10 enhances the replication of endogenous retroelements, but not exogenous retroviruses demonstrating that natural levels of MOV10 suppress retrotransposition. MOV10 overexpression decreases the level of HIV-1 genomic RNA packaged into nascent virions and also impacts the accumulation of reverse transcription products in target cells. The molecular mechanism/s by which MOV10 inhibits retroelements remains unclear, however, the anti-retroelement activities of MOV10 and APOBEC3 proteins are independent.Moreover, MOV10 is not essential for miRNA-mediated translation repression or slicer activity in cultured cells. In sum, ectopically overexpressed human MOV10 inhibits divergent exogenous and endogenous retroelements and, more significantly, the capacity of endogenous MOV10 to specifically suppress retrotransposition highlights it as a potential restriction factor of human retrotransposons in somatic cells.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2013

Author dc:creator

• Arjan-Odedra, Shetal

Advisors dc:contributor.advisor

• Malim, Michael Henry
• Martin Serrano, Juan
• Morris, Roger James

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/7ee91030-835b-4609-971e-f78e4e7aa0cc

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/7ee91030-835b-4609-971e-f78e4e7aa0cc