Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 239-251).

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The Wilms’ tumour suppressor gene WT1, encodes a structurally diverse and multifunctional protein with tightly controlled expression throughout the development of several organ systems. Although initially defined as a tumor suppressor, WT1 has been found to be overexpressed in some cancers. How WT1 contributes to the shift from normal to aberrant development, or from normal function to oncogenic function, is poorly understood. Recent studies have shown an abundance of bidirectional transcription across metazoan genomes suggesting that non-coding antisense transcripts may have important roles in cell function. WT1-AS transcripts are capable of positively modulating WT1 protein levels in vitro, but relatively little is known about the functions of these antisense transcripts in vivo. The aim of this thesis was to characterize the role of a highly conserved region, Mcr2, located upstream of human and mouse WT1. Our data suggests that Mcr2 is not translated into protein and is transcribed in an antisense orientation. Mcr2 was found partially conserved in fish and well conserved in terrestrial vertebrates. By analysing novel mouse strains with genetically modified Mcr2 we have identified that Mcr2 may have a role in both fertility and embryonic survival, as well as regulating liquid homeostasis in the adult mouse.

Sense-antisense transcripts (SATs) are messenger RNA (mRNA) transcripts that have regions that are complementary to regions of other mRNA transcripts. SATs may play an influential role in the regulation of gene expression. One evolutionary event that has had a dramatic impact on many genomes is the widespread dispersal of repetitive sequences which includes transposable elements (TEs) as well as simple and tandem repeats. Approximately 45% of the human and 37.5% of the mouse genomes are composed of repeats derived from transposable elements. A group of SATs was identified as resulting from transposable elements integrating into the coding strand of some genes and into the template strand of the coding region of other genes. These SATs may add to the complexity of an organism's regulatory network or they may be the result of rather recent TE activities yet to succumb to sequence divergence. The human, mouse and bovine genomes were analyzed for SATs using publicly available datasets and bioinformatics analysis tools. Each sense-antisense binding region (SABR) was aligned to transposable elements from the RepBase repeat database revealing many SABRs containing TE sequence in a large portion of the sequence. A Gene Ontology analysis on subsets of the data showed enrichments for the functional category of "DNA repair" and the component category "cytoplasm". An analysis of the substitution rates in human and mouse across the 3' UTRs of transcripts containing SABRs at the 5' end of their 3' UTRs showed that the substitution rate in the region of the SABR was lower than compared to the beginning of the 3' UTR. The lower percent GC composition found at the 3' end of the 3' UTRs could be attributed to conserved poly-A signals in this region.

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Tübingen, Universiẗat, Diss. 2008.

Thesis (Ph. D.)--Ohio State University, 2005. / Document formatted into pages; contains 375 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 March 9.