Start Date
11-12-2019 11:15 AM
Description
Abstract
Human T-lymphotropic virus type 1 (HTLV-1) affects roughly 10 million people worldwide, particularly in Japan, sub-Saharan Africa, the Caribbean, and South America (Futsch et al. 2017). Approximately 4% of infected individuals develop Adult T-cell Leukemia/Lymphoma (ATLL), and about 2% develop Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM) (Futsch et al. 2017). HTLV-1 is a retrovirus that ultimately seeks to replicate itself, which requires making many viral proteins (Martin et al. 2016). One way it makes these proteins is through ribosomal frameshifting. The frameshift site we are studying is the HTLV-1 gag-pro frameshift site, and it includes an RNA stem-loop structure (Caliskan et al. 2015). Stem-loops are formed by the base-pairing of RNA nucleotides in the transcript. The goal of the project is to investigate the relationship between HTLV-1 gag-pro programmed -1 ribosomal frameshift efficiency and the thermodynamic stability of the gag-pro frameshift site stem-loop. My research team hypothesizes that decreases in the stability of the stem-loop’s first three base-pairs will cause corresponding decreases in frameshift efficiency. We will test this hypothesis by designing several stem-loop mutants, each with varying stabilities relative to the wild-type structure, and measuring their frameshift efficiencies. Here, I propose how exactly these HTLV-1 gag-pro frameshift site mutants will be used to evaluate our hypothesis. Ultimately, our research will contribute to a gap in the understanding of how the HTLV-1 RNA structures promote virus replication.
Determining how Stem-Loop Structure Thermodynamic Stability Influences Frameshift Efficiency at the HTLV-1 gag-pro Frameshift Site
Abstract
Human T-lymphotropic virus type 1 (HTLV-1) affects roughly 10 million people worldwide, particularly in Japan, sub-Saharan Africa, the Caribbean, and South America (Futsch et al. 2017). Approximately 4% of infected individuals develop Adult T-cell Leukemia/Lymphoma (ATLL), and about 2% develop Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM) (Futsch et al. 2017). HTLV-1 is a retrovirus that ultimately seeks to replicate itself, which requires making many viral proteins (Martin et al. 2016). One way it makes these proteins is through ribosomal frameshifting. The frameshift site we are studying is the HTLV-1 gag-pro frameshift site, and it includes an RNA stem-loop structure (Caliskan et al. 2015). Stem-loops are formed by the base-pairing of RNA nucleotides in the transcript. The goal of the project is to investigate the relationship between HTLV-1 gag-pro programmed -1 ribosomal frameshift efficiency and the thermodynamic stability of the gag-pro frameshift site stem-loop. My research team hypothesizes that decreases in the stability of the stem-loop’s first three base-pairs will cause corresponding decreases in frameshift efficiency. We will test this hypothesis by designing several stem-loop mutants, each with varying stabilities relative to the wild-type structure, and measuring their frameshift efficiencies. Here, I propose how exactly these HTLV-1 gag-pro frameshift site mutants will be used to evaluate our hypothesis. Ultimately, our research will contribute to a gap in the understanding of how the HTLV-1 RNA structures promote virus replication.
Comments
Mentor: Kathryn Mouzakis