In biology, changes in structure are correlated to changes in function. This is true for cells, proteins, and nucleic acids. Though experimental techniques observe structure and function independently, there is still a gap in relating the two. This problem is increased in systems like RNA, which is able to fold into specific conformations and perform diverse functions. Recently, computational techniques predicted conformational changes in RNA structures, making them a promising strategy for addressing this issue. Here, we use computational and machine learning tools to relate structure and function, using a new synthetic RNA nanostructure, termed the Riboswitch-Nanostar Complex (RNC). This structure was designed by fusing two RNA structures: a multivalent nanostar and a riboswitch. The nanostar, chosen for its spatial and temporal modularity, is a synthetic multi-stranded structure that branches out of a central junction. The riboswitch, chosen for its binary functional outputs, is a biological RNA structure that can bind to a specific ligand and trigger gene expression changes. In this study we conducted molecular dynamics simulations of RNCs under various temperature and salt concentrations and developed predictive algorithms that used the feature-engineered data. Our findings reveal that structural metrics like contacts and potential energy can predict the functional output of the system. These results emphasize the strength of this tool and its potential to bridge structural and functional analysis.

This abstract has been withheld from publication.

This abstract has been withheld from publication.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, which is marked by abnormal accumulation of fat within the liver. However, the mechanism of disease progression is not fully understood. Previous studies have found that many different molecules are involved in the disease. Specifically, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) have been identified as critical components of liver inflammation and fibrosis. They can be regulated by a variety of other factors. Merlin is a crucial upstream regulator inhibiting YAP/TAZ activity. This study aims to elucidate the role of Merlin and its downstream effects through YAP/TAZ in MASLD. This study also aims to examine the effect of Oxy210, a synthetic oxysterol-based drug candidate, on MASLD. In previous studies, Oxy210 has been shown to inhibit pro-fibrotic pathways and preserve hepatic mitochondrial function. This study aims to examine if Oxy210 preserves OXPHOS proteins and if Oxy210 affects Merlin expression in the progression of disease. We used liver protein extracted from mouse MASLD models to characterize the protein expression in YAP/TAZ pathways. Our preliminary data demonstrate that Oxy210 does not affect Merlin level, but preserve OXPHOS proteins in the progression of MASLD. In a broader context, mechanistic insights from our study can contribute to the development of new drugs for MASLD and other liver diseases.

As cancer continues to be one of the leading causes of death worldwide, understanding and harnessing the functioning of key proteins involved in cancer progression can prove highly valuable. Spindlin proteins have been known to play an important role in cell cycle control. More specifically, Spindlin 3 (SPIN3) has been found to have tumor suppressor capabilities, but its mechanism is relatively understudied. Here we examined the localization and regulation of SPIN3 to understand its role as a tumor suppressor. Immunofluorescence imaging (IF) was conducted to identify SPIN3’s localization patterns throughout different phases of cell division. Its interaction with the PRMT5/MEP50 complex has also been visualized. Moreover, an inducible GFP-SPIN3 HeLa cell line along with inducible SPIN3 mutant cell lines were developed. We found that SPIN3 localizes to the microtubule organizing center (MTOC) and nuclear lamina region during interphase, and continues at the spindle pole region (specifically the pericentriolar material) during mitosis. Significant SPIN3 mis-localization after mutation was not detected through IF. Further in vitro binding experiments are required to study the interaction of SPIN3 with other proteins to confirm its potential role as a drug target for cancer therapy.