Poster abstracts
Poster number 82 submitted by Dana Beseiso
Investigating alternative Transcription Start Site (TSS) usage in breast cancer
Dana Beseiso (Department of Biological Chemistry, University of Michigan), Kesang Gawa (Department of Biological Chemistry, University of Michigan), Ben Pockrass (Department of Biological Chemistry, University of Michigan), Ritam Neupane, PhD (Department of Biological Chemistry, University of Michigan), Rachel Niederer, PhD (Department of Biological Chemistry, University of Michigan)
Abstract:
The expression of multiple messenger RNA (mRNA) isoforms by a singular gene is essential for promoting cellular diversity and adapting to stress. Alternative transcription start site (TSS) usage results in mRNAs that differ in their 5′-ends and, as a result, their 5′ untranslated regions (5′ UTRs). 5′ UTRs harbor translational control elements that modulate protein output, but it remains poorly understood whether alternative TSS usage is broadly employed as a mechanism to modulate protein abundance, especially throughout disease progression. We hypothesize that widespread changes in TSS usage drive translational reprogramming which promotes the cellular and morphological changes necessary for cancer progression. We show that the annotated 5′ UTR isoforms of the Breast Cancer Resistance Protein (BCRP) and the metastasis-associated proteins, NODAL, NANOG, and SNAIL, are differentially translated in vitro. Interestingly, we observe that the differences in translational output among 5' UTR isoforms vary in magnitude across extracts derived from different cancer cell lines. Further, we have identified a sequence element that appears to alter protein output differentially in extracts derived from HeLa cells versus mammary cell lines, suggesting there are likely context-specific regulatory features within 5′ UTRs. Finally, high throughput analysis of ribosome recruitment by a comprehensive list of human 5′ UTR isoforms reveals distinct enhancer and repressor motifs. Identifying novel translational control elements in 5′ UTRs will elucidate their role in modulating gene expression and inform novel anticancer therapeutic strategies.
Keywords: Alternative TSSs, 5 UTR Isoforms, Translational Control