Start Date
16-12-2020 9:20 AM
Description
Human T-Cell Leukemia Virus (HTLV-1) is a retrovirus that infects approximately five to ten million people across the world, with about 5% of those infections developing into adult T-cell leukemia (Gessain and Cassar 2012; Matsuoka and Jeang 2007). The HTLV-1 RNA genome includes two Programmed -1 Ribosomal Frameshift (-1 PRF) sites, which are critical for the synthesis of key enzymes needed for viral replication. Our lab recently demonstrated that an RNA structure called a pseudoknot is found in the 2nd frameshift site (Thulson et al. 2020). While we showed that the pseudoknot structure as a whole was important to frameshift stimulation, we don’t know which parts of this structure are critical to its function. Other studies on viruses that use pseudoknot structures to stimulate -1 PRF, such as Simian Retrovirus Type 1 (SRV-1), found that contacts between different parts of the structure were critical to pseudoknot function. The overall goal of my project is to identify similar types of contacts within the HTLV-1 pro-pol pseudoknot structure. I hypothesize that contacts between the nucleotides in the loops and base pairs in the stems, defined as base triples, form within the HTLV-1 RNA pseudoknot and that these contacts influence the frameshifting efficiency.
Investigating the Role of Base Triples in the HTLV-1 Pseudoknot
Human T-Cell Leukemia Virus (HTLV-1) is a retrovirus that infects approximately five to ten million people across the world, with about 5% of those infections developing into adult T-cell leukemia (Gessain and Cassar 2012; Matsuoka and Jeang 2007). The HTLV-1 RNA genome includes two Programmed -1 Ribosomal Frameshift (-1 PRF) sites, which are critical for the synthesis of key enzymes needed for viral replication. Our lab recently demonstrated that an RNA structure called a pseudoknot is found in the 2nd frameshift site (Thulson et al. 2020). While we showed that the pseudoknot structure as a whole was important to frameshift stimulation, we don’t know which parts of this structure are critical to its function. Other studies on viruses that use pseudoknot structures to stimulate -1 PRF, such as Simian Retrovirus Type 1 (SRV-1), found that contacts between different parts of the structure were critical to pseudoknot function. The overall goal of my project is to identify similar types of contacts within the HTLV-1 pro-pol pseudoknot structure. I hypothesize that contacts between the nucleotides in the loops and base pairs in the stems, defined as base triples, form within the HTLV-1 RNA pseudoknot and that these contacts influence the frameshifting efficiency.
Comments
Mentor: Kathryn Mouzakis