Author(s): Tyler Kline
Mentor(s): Hung Yu-Shih
Institution UTech
RNA Polymerase III (POLR3) is a critical enzyme responsible for transcribing DNA into small RNAs, such as tRNAs, 5S rRNAs, and U6 sRNAs, and is composed of 17 unique subunits. Mutations in subunits such as POLR3A, POLR3B, POLR3K, POLR3G, and POLR3GL have been linked to 4H leukodystrophy (4H), a heterogeneous group of inherited neurodegenerative disorders characterized by a wide range of phenotypes, including hypomyelination, hypogonadotropic hypogonadism, and hypodontia. Numerous mutations and variants associated with 4H have been documented through various clinical studies; however, no comprehensive effort has yet been undertaken to systematically summarize and annotate these mutations. This study aims to provide a thorough annotation of exon mutations identified in the 4H-associated genes POLR3A, POLR3B, POLR3K, POLR3G, and POLR3GL. We will begin by focusing on POLR3A, which encodes the largest subunit of POLR3. A schematic representation with direct annotations will be generated to map mutations within the POLR3A gene, including missense, nonsense, and splice site mutations identified from global patient studies through genomic analysis. These annotations will serve as a valuable resource for future research into the genetic basis and molecular mechanisms underlying 4H leukodystrophy.