IDENTIFICATION AND CHARACTERIZATION OF AN INTRONIC TRANSCRIPT FOR TLE1

Date

2024-8-28

Author

Yılmazbilek, İrem

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In a previous study, we used the high-output Nanopore sequencing technology (Oxford Nanopore Technologies, ONT) to identify novel isoforms that are regulated by Estradiol (E2) in an Estrogen Receptor (ER) positive breast cancer model cell line. The advantage of using ONT sequencing allowed the discovery of alternative isoforms, one of which was an intronically polyadenylated TLE (Transducin-like enhancer protein 1) isoform. TLE1 is known as a transcriptional corepressor in different contexts but also positively assists ER-chromatin interactions. In this thesis, I used a comprehensive approach to characterize this intronically terminated TLE1 isoform using Artificial Intelligence (AI) based computational modeling and wet lab experiments. The results of the study present evidence of the functional consequences of this mRNA isoform that is translated but is C’terminus truncated and lacks critical domains for protein interactions. Overall, our data show that a truncated TLE1 protein co-exists with the canonical protein and could play a role in ER chromatin interactions and alter E2 responsive gene regulation.

Subject Keywords

TLE1, Breast Cancer, Intronic Isoform, Protein Modeling, Nanopore

URI

https://hdl.handle.net/11511/111392

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Graduate School of Natural and Applied Sciences, Thesis