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dc.contributor.authorGardner, Joseph Michael
dc.date.accessioned2019-06-26T08:37:47Z
dc.date.available2019-06-26T08:37:47Z
dc.date.issued2019-10-26
dc.date.submitted2017-09-28
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/294025
dc.description.abstractRetrotransposons comprise approximately 40% of the mouse genome. Once thought to be useless “junk” DNA, there is growing evidence that retrotransposons play crucial roles in genome evolution and gene regulation, and contribute to the transcriptome. Several studies have found functional retrotransposon transcripts in the germline and during early development, but less is known about retrotransposon transcription in adult somatic cells. Retrotransposons are also responsible for generating gene copies in mammalian genomes (retrocopies), and there are several examples of retrocopies evolving into new genes, or being transcribed as non-coding RNA. Using computational approaches, I analyse RNA-seq data to assess the contribution of retrotransposons and retrocopies to the transcriptomes of adult mouse somatic cells, using purified naive B and T lymphocytes. First, I describe the transcriptomes generated using high-quality total RNA-seq data. Second, I quantify and characterise the retrotransposon content of these transcriptomes. Finally, I identify retrocopy transcripts and assess their relationship with the genes from which they originate. I found widespread inclusion of retrotransposons in somatic cell transcriptomes. These transcripts form distinct clusters based on retrotransposon sequence, with endogenous retroviruses being particularly prevalent in retrotransposon-rich transcripts. While these clusters are consistent between cell types, the individual retrotransposons transcribed show cell-type specificity. I also find evidence that retrotransposons may facilitate gene regulation by antisense transcripts. I demonstrate that a subset of retrocopies is transcribed, and the vast majority of these form RNA complementary to their parent mRNA, with high sequence identity. Using differential expression and proteome analysis, I present evidence for post-transcriptional regulation of parent transcripts by retrocopy RNA, possibly through stabilisation of the parent RNA. I also find that while retrocopy expression is not necessarily shared between cell types or mouse strains, certain parent transcripts tend to have an expressed retrocopy in multiple contexts. Overall, this thesis presents evidence of an important role for retrotransposons and retrocopies in the adult somatic transcriptome, and sets the stage for further investigation to experimentally elucidate the functions of these transcripts.
dc.description.sponsorshipFunded by the BBSRC
dc.language.isoen
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectbioinformatics
dc.subjectRNA-seq
dc.subjecttranscriptome
dc.subjectnon-coding RNA
dc.subjectncRNA
dc.subjectlong non-coding RNA
dc.subjectlncRNA
dc.subjectretrotransposon
dc.subjecttransposon
dc.subjecttransposable element
dc.subjectretrogene
dc.subjectretrocopy
dc.subjectpseudogene
dc.subjectRNA
dc.subjectsequencing
dc.subjectantisense
dc.subjectendogenous retrovirus
dc.subjectLINE
dc.subjectSINE
dc.subjectLTR
dc.subjecttranscriptomics
dc.subjectgenome
dc.subjectepigenetics
dc.subjectlymphocytes
dc.subjectmouse
dc.subjectgenetics
dc.titleThe Contribution of Retrotransposons to the Transcriptomes of Murine Somatic Cells
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentGenetics
dc.date.updated2019-06-25T14:40:54Z
dc.identifier.doi10.17863/CAM.41133
dc.publisher.collegeGirton
dc.type.qualificationtitlePhD in Genetics
cam.supervisorFerguson-Smith, Anne
cam.thesis.fundingtrue


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Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
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