IDENTIFICATION AND CHARACTERIZATION OF AN INTRONIC TRANSCRIPT FOR IGFBP4

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2023-1-20

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Yılmaz, Utku Cem

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Alternative polyadenylation is a widespread mRNA processing event affecting the length of the 3’UTR of mRNAs. Alternative use of polyadenylation sites sometimes occurs in terminal exons, proximal exons, or proximal introns, affecting the coding 3’UTR length and even the coding sequence of the mRNA. To identify estrogen (E2) related polyadenylation changes by a 3’-seq experiment, we detected an early intronic polyadenylation site for IGFBP4 (insulin-like growth factor binding protein 4). In this thesis, I present data to confirm the existence of an intronic transcript that is robustly upregulated in response to E2 exposure in estrogen receptor-positive breast cancer cell lines. The expression pattern for this isoform follows an opposite pattern to that of the full-length isoform. Hence, we focused on the initial characterization of this isoform. I confirmed the 3’-end of the transcript with an intronic novel poly(A) signal. I performed reporter assays to suggest the functionality of the candidate poly(A) signal compared to the poly(A) signal found at the 3’UTR of the canonical isoform. I provide additional insight into the characterization of the intronicly polyadenylated isoform including mRNA stability and coding potential. While the functional role of this isoform is still not clear, these results highlight the need to detect and investigate different isoforms that may originate from a gene locus.

Subject Keywords

Intronic Polyadenylation, IGFBP4, Alternative Polyadenylation, Breast Cancer

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https://hdl.handle.net/11511/102066

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

U. C. Yılmaz, “IDENTIFICATION AND CHARACTERIZATION OF AN INTRONIC TRANSCRIPT FOR IGFBP4,” M.S. - Master of Science, Middle East Technical University, 2023.