Poster abstracts
Poster number 18 submitted by Dana Beseiso
Investigating functional Transcription Start Site (TSS) switching in breast cancer
Dana Beseiso (Department of Biological Chemistry, University of Michigan), Rachel O. Niederer (Department of Biological Chemistry, University of Michigan)
Abstract:
Breast adenocarcinoma, the most common type of breast cancer, arises in epithelial cells of breast glands. Cancerous epithelial cells can undergo Epithelial to Mesenchymal Transition (EMT) allowing them to become more motile, invasive, and thus malignant. EMT is associated with genome-wide changes in the transcriptome, including alternative splicing and polyadenylation. However, changes in Transcription Start Site (TSS) usage, which defines the 5′ Untranslated Region (5′ UTR) of an mRNA, remain comparatively understudied. Given that 5′ UTRs may harbor translational control elements that alter ribosome recruitment to the mRNA, TSS switching can direct changes in gene expression and thus facilitate cellular reprograming. Here, we utilize the recently developed high throughput Direct Analysis of Ribosome Targeting (DART) to investigate and characterize translational control elements in breast cancer-specific 5′ UTRs at various EMT intermediate states. We anticipate that TSS switching will produce distinct 5′ UTRs that promote or inhibit translation, and thus facilitate EMT. Investigating alternative TSS usage and downstream translational control will enhance our understanding of translational regulation by 5′ UTRs as well as inform therapeutic targeting of pathogenic 5′ UTR isoforms.
References:
Niederer, R. O.; Rojas-Duran, M. F.; Zinshteyn, B.; Gilbert, W. V. Direct Analysis of Ribosome Targeting Illuminates Thousand-Fold Regulation of Translation Initiation. Cell Syst. 2022, 13 (3), 256-264.e3. https://doi.org/10.1016/j.cels.2021.12.002.
Keywords: 5 UTRs, EMT, Translational control