Characterizing heat shock-induced mRNA produced past the 3’ end of genes

Undergraduate Honors Thesis

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/x059c914s

Abstract

Mammalian transcription is a tightly controlled process for mRNA production. Cellular stress has been shown to impact several steps in transcription. For example, heat shock induces termination defects, causing dysfunctional termination of mRNA synthesis that may interfere with downstream genes and alter protein synthesis. It is unclear how malfunctioning termination machinery permits Pol II to continue transcribing past the normal 3’ end of mRNA genes, or how the RNA produced after failed termination impacts the cell. This is a pervasive biological phenomenon with unknown implications and is likely a fundamental biological process that will advance our understanding of cellular biology. This project aimed to investigate RNA produced during stress induced-termination defects through characterizing the 3’ cleavage that releases mRNA from RNA polymerase II (Pol II), the cellular localization of mis-terminated RNAs, and the stability of these RNA molecules. We found that RNA produced upon stress-induced termination defects can be characterized by having a general loss of 3’ cleavage, nuclear retention, and decreased stability compared to mRNA in unstressed cells. These findings provide insight into the mechanisms that give rise to termination defects, and the cellular fate of the transcripts that result.

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