Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains viii, 100 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 80-96).

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

Thesis (Ph.D. in Biophysics & Genetics, Human Medical Genetics Program) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 123-147). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb. 19, 2009). Includes bibliographical references (p. 71-80).

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed on June 24, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / "July 1998." Typescript. Vita. Includes bibliographical references (leaves 215-225). Also available on the Internet.

Retroviruses have evolved sophisticated mechanisms to ensure timely export of incompletely spliced viral messenger ribonucleic acids (mRNAs) for gene expression and for viral packaging. For example, the Human Immunodeficiency Virus type 1 (HIV-1) encodes the Rev regulatory protein, a sequence-specific RNA-binding protein that is responsible for the cytoplasmic accumulation of intron-containing viral mRNAs. The HIV-1 Rev protein contains an amino terminal (N-terminal) Arginine-Rich Motif (ARM) RNA-binding domain (RBD) and a carboxy terminal (C-terminal) leucine-rich activation domain which functions as a Nuclear Export Signal (NES). The Rev ARM interacts in a sequence-specific manner with a cis-acting viral RNA stem-loop structure, the Rev Responsive Element (RRE), located in all incompletely spliced viral mRNAs. This initial interaction is followed by the recruitment of additional Rev molecules to form a RiboNucleoProtein (RNP) complex involving the RRE and Rev molecules. The cytoplasmic accumulation of the Rev:RRE RNP complex is dependent on the interaction of Rev with key cellular cofactors. Rev activation domain mutants exhibit a trans-dominant negative phenotype, suggesting that this domain of Rev interacts with cellular proteins required for Rev function. Biochemical and genetic studies have identified several cellular proteins that bind to the activation domain of Rev and are therefore candidate cofactors for Rev function. Amongst these is the human Rev Interacting Protein [hRIP, 79], which is also known as the Rev/Rex activation domain-binding protein [Rab, 18]. hRIP was identified in a yeast two-hybrid assay with the HIV-1 Rev and its functionally equivalent Human T-cell Leukemia Virus type-1 (HTLV-1) Rex protein as baits. The interaction between hRIP and HIV-1 Rev is dependent on a functional Rev NES, as predicted for a bona fide Rev cellular cofactor, and the Nucleoporin-like (Nup-like) repeats in the C-terminus of hRIP (18, 79]. Additional genetic studies indicated that the interaction between hRIP and Rev is indirect and is most likely mediated by the cellular export receptor CRM1 (Chromosomal Region Maintenance 1) [1, 153]. A role for hRIP in Rev function or HIV-1 replication has remained elusive. The goal of this dissertation was to determine whether hRIP is required for Rev function and HIV-1 replication. We used two approaches, a dominant-negative mutant and RNA interference (RNAi), to ablate hRIP activity and analyzed Rev function and HIV-1 replication using standard assays. The results of this dissertation demonstrate that hRIP is required for Rev function and HIV-1 replication. We show that Rev function is inhibited upon ablation of hRIP activity by either a trans-dominant negative mutant or RNAL Furthermore, we find that depletion of endogenous hRIP by RNAi results in the loss of viral replication in human cell lines and primary human macrophages. Unexpectedly, in the absence of functional hRIP, RRE-containing viral RNAs accumulate in the nuclear periphery where hRIP is localized. Comparable ablation of hRIP activity did not affect the intracellular localization or trafficking of a variety of proteins or cellular poly (A+ mRNA, suggesting that the inhibition of Rev-directed RNA export is specific. In conclusion, the results of this dissertation demonstrate that hRIP is involved in the movement of Rev-directed RNAs from the nuclear periphery to the cytoplasm. Therefore, hRIP is required for Rev function and HIV-1 replication. The hRIP protein is not essential for the maintenance of cell viability and thus might represent a novel target for the development of antiviral agents for HIV-1.

Serine/Arginine splicing factor 1 (SRSF1), a member of the Serine/Arginine rich (SR) RNA-binding proteins (RBPs) family, regulates mRNA biogenesis at multiple steps and is deregulated in cancer and autoimmune diseases. Preliminary studies show that members of the SR protein family play a role in cellular transcription. We investigated SRSF1’s role in cellular gene transcription utilizing time-course RNA-Seq and nuclear run-on assays, validating a subset of genes transcriptionally regulated following SRSF1 overexpression. Pathway analysis showed that genes in the TNF/IL17 pathways were enriched in this dataset. Furthermore, we showed that MyD88, a strong activator of TNF transcription through transcription factors NF-κB and AP-1, is a primary target of SRSF1’s transcriptional activity. We propose that SRSF1 activates the transcription factors NF-κB and AP-1 through MyD88 pathway. SRSF1 overexpression regulates several genes that are deregulated in malignancies and immune disease, suggesting a role for SRSF1’s transcriptional activity in oncogenesis and immune response regulation. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

Diabetic nephropathy (DN) is one of the leading causes of end stage renal disease (ESRD) in western world and has a trend to spread in developing countries. Pathogenesis of DN is not fully elucidated. Studies of recent years showed that podocyte loss and activation of the rennin-angiotensin system (RAS), especially intra-renal RAS, played important roles in this process. Although renal biopsy is currently the most common way used to determine the expression pattern of podocyte and RAS associated molecules in DN, this invasive procedure has its own risk and is not practical for serial monitoring. We hypothesized that measurement of messenger ribonucleic acid (mRNA) expression of related genes in the urinary sediment might be a useful way to assess the severity of DN. / Firstly, we found that urinary mRNA expressions of podocyte-associated molecules nephrin, podocin, synaptopodin, Wilm's tumor-1 (WT-1) and alpha-actinin-4 were higher in patients with DN than in healthy controls, and urinary nephrin, podocin and synaptopodin expression was related to proteinuria and baseline renal function. In addition, there was a close relationship between urinary mRNA expression of type 2 angiotensin converting enzyme (ACE2), a key element of RAS, and the degrees of proteinuria, renal function and rate of decline of glomerular filtration rate (GFR). Urinary mRNA expression of ACE also inversely correlated with the rate of renal function decline. / In the next step, we studied the change in urinary mRNA expression of nephrin, podocin, synaptopodin, ACE and ACE2 in patients with DN treated with angiotensin converting enzyme inhibitor (ACEI) and addition of angiotensin receptor blocker (ARB). We found that urinary mRNA expression of podocin, synaptopodin and propably nephrin increased with disease progression, and percentage change in urinary podocin expression negatively correlated with rate of decline of GFR. Furthermore, serial measurement of urinary expression of nephrin and possibly synaptopodin may reflect therapeutic response to ARB in these patients. Urinary mRNA expression of ACE and ACE2, however, remained unchanged during the study duration and did not correlate with therapeutic response. / In this series of work, we investigated (i) the relation between the gene expression profile of podocyte-associated molecules and RAS related molecules in the urinary sediment and the severity of DN, including clinically defined parameter of disease severity, histological scarring, and the degree of intra-renal podocyte loss, (ii) the relation between urinary and intra-renal gene expression of patients with DN, (iii) the application of urinary gene expression on the monitoring of disease progression and therapy response of DN. The urinary mRNA expression of related genes was quantified by real-time quantitative polymerase chain reaction (RT Q-PCR). The intra-renal mRNA expression of related genes was studied from the histologic specimens of kidney biopsy by laser catapult microdissection (LCM) and RT Q-PCR. The degree of renal scarring was determined by morphometric analysis. Glomerular podocyte number was determined by stereological study on serial sections of renal biopsy specimen. / Taken together, our results suggest that although urinary mRNA expression of podocyte and RAS associated molecules is not related to intra-renal expression, urinary expression has the potential to be used as a non-invasive tool to assess the severity and progression of DN, and serial measurements of urinary gene expression of podocyte associated molecules may be used to reflect therapy response for patients with DN. Our findings also indicate that the information from urinary gene expression is supplementary to, but not a surrogate of, the data obtained from renal biopsy. / We then examined the relation between urinary gene expression and histological changes in the kidney. We found that urinary WT-1 expression correlated with the degree of kidney fibrosis. Unlike intra-renal expression, urinary mRNA expression of podocyte associated molecules did not correlate with glomerular podocyte number. There was also no association between urinary and intra-renal mRNA expression. / Wang, Gang. / Adviser: Cheuk Chen Szeto. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3423. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 156-180). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.