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The fate of RNA and RNA binding proteins in Sindbis virus infection

Ni, Shuai

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Abstract

RNA binding proteins (RBPs) accompany RNA throughout its whole life cycle. Therefore, the interaction of RBPs and target RNAs is particularly essential for post-transcriptional regulation. Not only can RBPs affect the RNA’s expression, they can also control the localization, degradation, translation, and other activities of RNA. Capitalizing on recent advances in high-throughput sequencing, this thesis describes the use of transcriptomic and proteomic technologies to systematically study the interplay of RNA and RBPs under the context of viral infection. In brief, we infect the human cell line HEK293 with the Sindbis RNA virus, with the aim of demonstrating how the viral infection remodels the host transcriptome and proteome. While it is commonly accepted that RBPs play a role in the regulation of gene expression, their contributions are still poorly understood. By using RNA interactome capture to track dynamic changes in RNA-binding proteome along the course of viral infection of Sindbis virus in human cells, we aim to assess the global impact of Sindbis virus infection on host transcriptome and proteome, and to identify host RBPs that interact with the Sindbis virus during its reproduction. This thesis reviewed the interplay dynamics between RNA and RBPs in human HEK293 cell line at three different viral infection stages. We observed a remodelling of binding activities of RBPs and the subsequent activation of the immune responses in the host cell. To our surprise, most RBPs demonstrating altered RNA binding did not show protein-level changes. Besides using statistical methods to evaluate the relative effects of different RNA processes, we also demonstrated that RNA degradation pathways had the biggest contribution to changes in RNA abundance change in SINV infected cells. Similar machinery may also apply to other alphaviruses, such as Chikungunya and Mayaro viruses, and thus we hope this study may contribute for the development of drugs to help solving public health problems caused by similar viruses in around the world.

Item Type: Dissertation
Supervisor: Brors, Prof. Dr. Benedikt
Place of Publication: Heidelberg
Date of thesis defense: 13 July 2020
Date Deposited: 11 Aug 2020 07:37
Date: 2020
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
Subjects: 004 Data processing Computer science
Controlled Keywords: Sindbis-Virus, RNA, Bioinformatik
Uncontrolled Keywords: Transcriptome sequencing, Proteomics, Sindbis Virus
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