Analyzing the Effects of Single Nucleotide Polymorphisms on hnRNPA2/B1 Protein Stability and Function: Insights for Anticancer Therapeutic Design

Abstract

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is a pivotal player in m6A recognition, RNA metabolism, and antiviral responses. In the context of cancer, overexpression of hnRNPA2/B1, abnormal RNA levels, and m6A depositions are evident. This study focuses on two significant nonsynonymous single nucleotide polymorphisms (nsSNPs) within hnRNPA2/B1, namely, F66L and E92K. Our structural analyses reveal decreased stability in these mutants, with E92K being predicted to undergo destabilizing post-translational methylation. Furthermore, our extensive analysis of 44,239 tumor samples from the COSMIC database uncovers that amino acid position 92 exhibits the second-highest mutation frequency within hnRNPA2/B1, particularly associated with breast and lung cancers. This experimental data aligns with our theoretical studies, highlighting the substantial impact of the nsSNP at position 92 on hnRNPA2/B1's stability and functionality. Given the critical role of pre-mRNA splicing, transcription, and translation regulation in cellular function, it is important to assess the impact of these nsSNPs on the stability and function of the hnRNPA2/B1 protein to design more efficient anticancer therapeutics.

Lipid metabolism disorder in diabetic kidney disease

“…Computer modeling and simulation technologies are now pivotal in identifying therapeutic targets for diseases like cancer, liver fibrosis, and Takotsubo syndrome (TTS) ( 225 – 230 ). Future studies can leverage cost-effective methods like quantitative lipid analysis with ES-MSI and incorporate molecular dynamics (MD) simulations alongside computational bioinformatics to investigate lipid metabolism’s role in diabetic kidney disease (DKD) and natural drug effects on lipid disorders.…”