An Investigation of poly(A) site selection loci in estrogen treated breast cancer cells

Bekar, Damla
Alternative polyadenylation (APA) is an mRNA processing step implicated in 3’UTR (Untranslated Region) isoform diversity, which may have significant impacts on protein levels. Nearly 70% of known human genes harbor multiple polyA sites. Proliferative signals, developmental cues and tissue specificity can induce alternative selection of polyA sites, producing transcripts with different 3’UTR lengths. Given that APA generates a vast isoform diversity, there are possible mechanistic explanations emerging on how APA might be regulated. To better understand the APA mechanism in the presence of proliferative signals, we chose a model system where we know APA is induced by Estradiol (E2) in Estrogen positive (ER+) breast cancer cell line. We analyzed existing Chromatin Immunoprecipitation- Sequencing (ChIP- Seq) data for certain histone marks that may overlap with polyA sites in E2 treated cells and performed experiments to confirm usage of these specific polyA sites. Despite the low number of cases we could analyze in this study, our results may suggest a possible link between E2 regulated transcription and APA. Future high throughput experiments will be important to test how widespread these correlations are and what the underlying mechanisms are.


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Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is an RNA-binding protein with a broad range of functions including transcriptional and translational regulation of mRNAs, transport of mRNAs from the nucleus, alternative splicing, telomere maintenance, and miRNA processing. Among all, miRNA related functions of HNRNPA1 are the least understood. Hence, in this study, we aim to investigate potential miRNAs regulated by HNRNPA1.Using HNRNPA1-silenced MCF7 cells, we identified several notable miRNAs using N...
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Intracellular phenomena such as promoter strength, mRNA secondary structure, translation efficiency and codon preference, 5′-untranslated region processing, and protein turnover, have impacts directly on the expression of heterologous genes. Design of multi-promoter expression systems with constituent strong promoters and engineered promoter variants is a novel metabolic engineering strategy for increasing the promoter strength further, and tuning the expression for recombinant protein (r-protein) productio...
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Use of an intronic polyadenylation site in breast cancer
Köksal Bıçakcı, Gözd; Erson Bensan, Ayşe Elif; Department of Molecular Biology and Genetics (2020)
Alternative polyadenylation is an important mRNA processing step in which the length and/or the sequence of 3’UTR of mRNAs are altered. This change in 3’UTRs may have significant effects on mRNA stability, localization and translational efficiency. One of the APA types, called intronic polyadenylation (IPA), occurs on intronic sites rather than 3’UTRs. Recent evidence shows that almost 20% of human genes have a poly(A) site in at least one intron. In fact, some introns even may have more than one poly(A) si...
Citation Formats
D. Bekar, “An Investigation of poly(A) site selection loci in estrogen treated breast cancer cells,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Biology., Middle East Technical University, 2019.