Author(s): Kasia Poulson
Mentor(s): Hung Yu Shih
Institution UTech
RNA Polymerase III (POLR3) is essential for the transcription of small housekeeping RNAs and is crucial for cell viability. The Pol III subunit POLR3G plays a significant role in maintaining transcription, particularly in pluripotent stem cells, and mutations in this gene have been linked to disorders of the central nervous system (CNS), such as 4H leukodystrophy. Despite its importance, the specific role and regulatory mechanisms of POLR3G expression in CNS pathology remain unclear. Previous mouse knockout models for Polr3g have shown that Polr3g is highly expressed in pluripotent stem cells and is critical for early embryonic development. Deficiency in POLR3G results in embryonic lethality, hindering access to investigate the function of POLR3G in early postnatal events such as myelin formation, a key feature of 4H leukodystrophy. Zebrafish, with their genomic similarities to humans and the transparency of early-stage embryos, present a valuable model for in vivo study of gene function. Here, we aim to establish a zebrafish model of Polr3g deficiency through the morpholino approach to knock down the Polr3g protein expression. We will focus on the impacts of Polr3g function in the CNS by analyzing the markers of distinct neural cell types and developmental status. Moreover, we will address the cellular responses, such as proliferation and apoptosis. Our findings will reveal the specific role of Polr3g in developing CNS and with broader implications for understanding Polr3g in 4H pathogenesis.