Poster abstracts
Poster number 16 submitted by Dana Beseiso
Investigating functional transcription start site switching in breast cancer
Dana Beseiso (Biological Chemistry, University of Michigan ), Dr. Rachel Niederer (Biological Chemistry, University of Michigan )
Abstract:
Alternative transcription start sites (TSS) direct the majority of transcript diversity across tissues. Alternative TSSs can give rise to transcripts with 5′ Untranslated Region (5′ UTR) isoforms. Since 5′ UTRs often harbor regulatory elements that alter ribosome recruitment to mRNAs, these isoforms may drive differential translation facilitating translational reprogramming, a hallmark of cancer. Using luciferase reporters, we show that annotated 5′ UTR isoforms of the metastasis-associated proteins, NODAL, NANOG, and SNAIL, are differentially translated in human cancer extracts and identify novel translational control motifs. To map global 5′ UTR isoforms in a disease context, we utilize a series of breast cancer cell lines representing increasingly aggressive cancer states and perform ReCappable-seq. We anticipate that widespread TSS switching throughout metastatic progression will produce distinct 5′ UTR isoforms that alter translational output via enhancer or repressor motifs. Identifying novel translational control elements in 5′ UTRs will elucidate the 5′ UTR regulatory code and inform novel anticancer therapeutic strategies.
Keywords: 5 UTRs, Translational Control, TSS Switching