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Comprehensive Analysis of Factors Affecting Subcellular RNA Localization
Thesis

Comprehensive Analysis of Factors Affecting Subcellular RNA Localization

Kat Chin, Sydney McFarland, Sebastian Kadener and Ane Martin Anduaga
Bachelor of Science (BS), Brandeis University
04/2026
DOI:
https://doi.org/10.48617/etd.1533

Abstract

Splicing Alternative Splicing Splicing Efficiency mRNA Cytoplasmic Stability 3' UTR RNA

Throughout its life cycle, an mRNA molecule travels through different parts of the cell, beginning in the nucleus at the site of transcription in the chromatin before eventually reaching the cytoplasm, where it is translated, further localized, and eventually degraded. A diverse array of regulatory mechanisms affects the rates of the various processes occurring in each cellular compartment. Thus, the relative steady-state concentrations of mRNA in two major cellular compartments: the cytoplasm and chromatin, can be used to assess the different gene expression regulatory pathways operating within the cells. Here, we comprehensively analyze the relative expression of RNAs across the chromatin and cytoplasm in the heads of Drosophila melanogaster at three different ages. From this, we identified several key regulatory points. First, we identify a subset of RNAs that remain highly chromatin associated. These RNAs are longer transcripts and exhibit slowly-spliced introns that limit the rate of the overall splicing reaction, resulting in the accumulation of incompletely-spliced transcripts at sites of transcription on the chromatin. A second subset of these chromatin-enriched mRNAs display efficient splicing but very short cytoplasmic half-lives. These RNAs possess longer 3’ untranslated regions (UTRs) harboring destabilizing elements that induce degradation. Last but not least, we identified a cluster of transcripts, which included a substantial number of genes implicated in metabolic processes, whose relative cytoplasmic to chromatin-bound expression changed with age. This raises the possibility that transcript localization can be used as a biomarker for age.

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kat chin thesis5.81 MB
Embargoed Access, Embargo ends: 04/01/2028

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