Presentation Title

Determining how Stem-loop Structure Thermodynamic Stability Influences Frameshift Efficiency at the HTLV-1 gag-pro Frameshift Site

Faculty Mentor

Kathryn Mouzakis

Start Date

23-11-2019 8:00 AM

End Date

23-11-2019 8:45 AM

Location

115

Session

poster 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) affects roughly 10 million people worldwide, particularly in Japan, sub-Saharan Africa, the Caribbean region, and South America (Futsch et al. 2017). Approximately 2 to 4% of infected individuals develop Adult T-cell Leukemia/Lymphoma (ATLL), and about 1 to 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. One way it makes a subset of these proteins is through ribosomal frameshifting. The frameshift site we are studying is called the HTLV-1 gag-pro frameshift site, and it includes an RNA stem-loop structure. Stem-loops are formed by the base-pairing of the RNA nucleotides in the transcript. It is unknown how the stability of this stem-loop affects the frequency of frameshifting. 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. Our research team hypothesized that decreases in the stability of the stem-loop’s first three base-pairs would cause corresponding decreases in frameshift efficiency. We will test this hypothesis by varying the base-pair composition of the stem-loop and evaluating its impact on frameshift efficiency. Several stem-loop mutants were designed, each with varying stabilities relative to the wild-type structure. Each mutant is predicted to decrease frameshifting to a different degree. Here, we present preliminary research using a subset of these HTLV-1 gag-pro frameshift site mutants 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.

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Nov 23rd, 8:00 AM Nov 23rd, 8:45 AM

Determining how Stem-loop Structure Thermodynamic Stability Influences Frameshift Efficiency at the HTLV-1 gag-pro Frameshift Site

115

Human T-cell lymphotropic virus type 1 (HTLV-1) affects roughly 10 million people worldwide, particularly in Japan, sub-Saharan Africa, the Caribbean region, and South America (Futsch et al. 2017). Approximately 2 to 4% of infected individuals develop Adult T-cell Leukemia/Lymphoma (ATLL), and about 1 to 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. One way it makes a subset of these proteins is through ribosomal frameshifting. The frameshift site we are studying is called the HTLV-1 gag-pro frameshift site, and it includes an RNA stem-loop structure. Stem-loops are formed by the base-pairing of the RNA nucleotides in the transcript. It is unknown how the stability of this stem-loop affects the frequency of frameshifting. 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. Our research team hypothesized that decreases in the stability of the stem-loop’s first three base-pairs would cause corresponding decreases in frameshift efficiency. We will test this hypothesis by varying the base-pair composition of the stem-loop and evaluating its impact on frameshift efficiency. Several stem-loop mutants were designed, each with varying stabilities relative to the wild-type structure. Each mutant is predicted to decrease frameshifting to a different degree. Here, we present preliminary research using a subset of these HTLV-1 gag-pro frameshift site mutants 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.