@article{Modifications:7498,
      recid = {7498},
      author = {Wylder, Adam},
      title = {Messenger RNA Modifications and Reader Proteins in the  Regulation of Gene Expression},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2023-08},
      pages = {138},
      abstract = {Gene expression is regulated through a dynamic  interconnected web of systems with its rich complexity only  further appreciated following the Human Genome Project. The  genome by itself not containing all information on a  biological state has led to growing interest in the  regulation of its expression, including through chemical  modification deposited within mRNA transcripts. Here, I  explore the impact of the two most abundant mRNA  modifications, N6-methyladenosine (m6A) and pseudouridine  (Ψ) on gene expression by study of modification writer and  reader enzymes, which respectively deposit and interact  with transcript modifications.  In Chapter 2, I show how  m6A reader protein hnRNPG can accommodate mutual,  co-transcriptional interactions with RNA Polymerase II and  m6A-modified RNA through development of a spin-down assay  for low-complexity protein interactions. In Chapter 3, I  demonstrate that type I reader protein YTHDC1 interacts  with RNA Polymerase II through its structured YTH-domain,  which is outcompeted by its canonical ligand in m6A. In  Chapter 4, I perform a bioinformatic survey on the  connection between m6A writers and readers on tRNA. In  Chapter 5, I detail our newly developed NanoSPA platform  for direct, simultaneous long-read sequencing of m6A and Ψ  along the same mRNA transcript. Using this platform, we  demonstrate crosstalk between m6A and Ψ on modification  concurrence and translational efficiency. Together, the  work here expands the mechanistic understanding of mRNA  modification writers and readers in regulation of gene  expression.},
      url = {http://knowledge.uchicago.edu/record/7498},
      doi = {https://doi.org/10.6082/uchicago.7498},
}