Files
Abstract
Ribonucleic acids (RNAs) are abundant macromolecules that are distributed in almost all cellular compartments. Like proteins, they are composed of canonical building blocks and chemical modifications add another layer of regulation complexity to their cellular functions. The field of epitranscriptomics stemmed from studies of chemical modifications on RNAs. However, previous work mainly focused on how RNA modifications act in cis to alter the fate of RNAs themselves, such as translation, decay, and subcellular localization. RNAs can also act in trans to regulate other biomolecules. In this thesis, we present works with a focus on how RNA modifications orchestrate their functions as cellular activity regulators. In cytosol, RNAs can be critical regulators of phase-separated RNP granules to regulate translation activation in cultured neurons, brain organoids, and cell lines. When associated with chromatin, RNAs can direct region-specific histone deubiquitination to regulate gene expression in normal hematopoiesis maintained by TET2. Cellular RNAs can also function as sensors to ultraviolet irradiation through U-rich sequences to regulate SOX2-dependent expression of genes critical to cutaneous squamous carcinoma progression. Altogether, our discoveries provide evidence of the importance and prevalence of RNA modification affects the functions of trans-acting regulatory RNAs.