The RNA Binding Protein, Nab2, Regulates the Expression of the Extracellular Matrix Binding Domain of Dystroglycan: Implications for Intellectual Disability and Muscular Dystrophy

Authors

Allison PaschackFollow

Abstract

Nab2, the D. melanogaster functional ortholog of human ZC3H14, is an RNA binding protein associated with intellectual disability and has been shown to regulate splicing of genes in the developing Central Nervous System (CNS). Correct splicing of genes throughout the body and in the CNS is crucial for organismal development. The spliceosome works in conjunction with RNA binding proteins to ensure pre-mRNA is properly processed into mature mRNA before being translated into functional protein. One specific gene that Nab2 has been shown to regulate is the muscular dystrophy associated protein, Dystroglycan (Dg). In this independent study project, we find that when Nab2 is knocked out of the fly, Dg protein expression patterns change so that isoform D, which contains a domain that binds to the extracellular matrix, is expressed at very low levels. As flies lacking Dg display similar brain maldevelopment patterns to those lacking Nab2, we also looked at the brain structure from flies that were heterozygous for both Nab2 and Dg but found no significant differences from wildtype flies, or flies that were heterozygous for Nab2 only. It is hypothesized that this is likely due to phenotypes arising from the combined impact Nab2 has on expression of around 500 RNAs, so knocking down expression of Nab2 and only one other related protein is not enough to produce phenotypes. Future projects will work to better understand the relationship between Nab2 and the genes mis-spliced in its absence, such as RBFOX1, which also regulates alternative splicing. Work like this will elucidate how many genes Nab2 is interacting with directly, versus how many genes are downstream in a Nab2-regulated pathway.

Advisor

Regan, Erzsébet

Department

Biochemistry and Molecular Biology

Recommended Citation

Paschack, Allison, "The RNA Binding Protein, Nab2, Regulates the Expression of the Extracellular Matrix Binding Domain of Dystroglycan: Implications for Intellectual Disability and Muscular Dystrophy" (2024). Senior Independent Study Theses. Paper 11227.
https://openworks.wooster.edu/independentstudy/11227

Disciplines

Cell and Developmental Biology | Developmental Neuroscience | Disease Modeling | Genetics and Genomics | Molecular and Cellular Neuroscience | Musculoskeletal Diseases | Nervous System Diseases

Keywords

RNA binding protein, spliceosome, intellectual disability, muscular dystrophy, mushroom body, genetics, developmental biology

Publication Date

2024

Degree Granted

Bachelor of Arts

Document Type

Senior Independent Study Thesis