@article{THESIS,
      recid = {5222},
      author = {Sepich, Caraline Lee},
      title = {Location-Dependent Effects of N6-methyladenosine on mRNA  Translation and Stability},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2022-12},
      number = {THESIS},
      pages = {199},
      abstract = {Chemical modifications on RNA play critical roles in gene  expression regulation. Although recent advancements have  allowed for significant elucidation of their functions,  challenges remain in the understanding of their functional  effects and the mechanisms involved, and it is becoming  increasingly apparent that it is essential to consider the  role of the context. Using N6-methyladenosine (m6A) as an  example, I explore as a fundamental aspect of context the  role of the modification’s location in shaping its  function, including the type of RNA on which it is located,  its position on the RNA molecule, and the location of the  methylated RNA within the cell. First, I present a study  characterizing the METTL5-TRMT112 complex which deposits  m6A on 18S rRNA. I show that TRMT112 is required for METTL5  stability and that loss of METTL5 regulates gene expression  at the translational level, and discuss how the position of  the m6A site on 18S rRNA near the decoding center  influences its functional roles. Then, I examine the  relationship between m6A location and mRNA transcript  stability. I show through analysis of public data that m6A  in the 5’UTR is associated with increased stability, and  that this effect is reduced by depletion of YTHDF2. I  further investigate the role of all three YTHDF proteins in  transcript stability, revealing that triple knockdown  causes extensive transcriptome dysregulation, potentially  explained by increased P body formation. In aggregate, this  work underscores the importance of location in m6A  function, highlighting the necessity of considering a  modification’s context to elucidate its cellular function.},
      url = {http://knowledge.uchicago.edu/record/5222},
      doi = {https://doi.org/10.6082/uchicago.5222},
}