University Honors

Microexons (MICs) are a class of highly conserved 3-27 nucleotide-long alternatively splicedneuron-specific exons that display a switch-like regulation dynamically embedded into theprocesses of neuronal differentiation and may modify interaction domains of proteins.Understanding MICs is critical as misregulation of MICs has been strongly linked withneurodevelopmental disorders, particularly autism spectrum disorders (ASD). Thus, our currentinvestigation works to understand the MIC in the enzyme pseudouridine synthase 7 (PUS7), amember of a family of enzymes that pseudouridylates RNA through RNA-guided mechanisms.Pseudouridylation is the isomerization of uridine (U) to pseudouridine (Ψ) and is the most commonpost-transcriptional modification of RNAs. The process of pseudouridylation leads to an increasein RNA stability and more efficient base stacking. PUS7 was found to be integral to metabolichomeostasis, cell growth, and regulation of translation. Based on preliminary data, we have foundthat of the two isoforms of PUS7, the longer, MIC-including isoform (PUS7L), is almostexclusively expressed in the central nervous system (CNS), while the shorter isoform excludingthe MIC (PUS7S) is prevalent throughout the body. We utilized a mixture of behavioral (OpenField, Elevated Plus Maze, EEGs, and 3 Chamber Sociability/Social Novelty) and biochemical(iCLIP, Pseudo-Seq, and RT-PCR) assays on cell lines and our knock out PUS7MIC(-/-) mousemodel with the goal of shedding new light on the role of MICs, and uniquely, pseudouridylationin neuronal development and regulation, giving insight into the development of ASD caused byabnormal MIC regulation.