Investigation of the Polyprimidine Tract-Binding Protein-Associated Splicing Factor (PSF) Domains Required for the Hepatitis Delta Virus (HDV) Replication

Investigation of the Polyprimidine Tract-Binding Protein-Associated Splicing Factor (PSF) Domains Required for the Hepatitis Delta Virus (HDV) Replication

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Title: Investigation of the Polyprimidine Tract-Binding Protein-Associated Splicing Factor (PSF) Domains Required for the Hepatitis Delta Virus (HDV) Replication
Author: Al-Ali, Youser
Abstract: The hepatitis delta virus (HDV), composed of ~1,700nt, is the smallest circular RNA pathogen known to infect humans. Understanding the mode of replication of HDV implies on investigating the host proteins that bind to its genome. The polypyrimidine tract-binding protein-associated splicing factor (PSF), an HDV interacting protein, was found to interact with the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), and to facilitate the interaction of RNA transcripts with the CTD of RNAPII. Both PSF and RNAPII were found to interact with both polarities of the terminal stem loop domains of HDV RNA, which possess RNA promoter activity in vitro. Furthermore, PSF and RNAPII were found to simultaneously interact with HDV RNA in vitro. Together, the above experiments suggest that PSF acts as a transcription factor during HDV RNA replication by interacting with both the CTD of RNAPII and HDV RNA simultaneously. PSF knockdown experiments were performed to indicate that PSF is required for HDV RNA accumulation. Mutagenesis experiments of PSF revealed that HDV RNA accumulation might require the N terminal domain, and the RNA recognition motifs RRM1 and RRM2. I propose that the RRM1 and RRM2 domains might interact with HDV RNA, while the N-terminal domain might interact with the CTD of RNAPII for HDV RNA accumulation. Together, the above experiments provide a better understanding of how an RNA promoter might be recognized by RNAPII.
Date: 2011
URI: http://hdl.handle.net/10393/20317
Supervisor: Pelchat, Martin
Faculty: Médecine / Medicine
Degree: MSc

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