Biology subjects

Cho, S. S.

Publications and source records attributed to Cho, S. S..

4 recordsLinked to original sources

bioRxiv2026

Genetic comparisons of interleukin-17 reveal a framework for complex signaling evolution

The interleukin-17 (IL-17) family of cytokines comprises structurally distinct ligands and receptors which mediate immune responses at mucosal surfaces. The growing understanding of its regulatory functions beyond immunity, together with extensive genetic variation in protein-coding genes, raises the possibility that IL-17 cytokines participate in an even wider network of biologic processes. Despite successes of experimental approaches to chart IL-17 functions, inherent signaling complexities and crosstalk with multiple physiologic pathways obscure a full appreciation of the biological potential of IL-17. Here, we integrated comparative genomics, evolutionary rate covariation (ERC), and signatures of natural selection to resolve phylogenetic relationships between IL-17 ligands and receptors and discovered evidence for hidden signaling interactions. ERC analysis revealed putative ligand-receptor interactions for IL-17D and IL-17RC and suggested uncharacterized potential signaling mediator for the receptor IL-17REL, such as IL-17B. Signals of covariation extended beyond the IL-17 family to other genes encoding neurodevelopmental effectors and growth factors, emphasizing recurrent co-evolutionary patterns that delineate the immune and neuromodulatory roles of IL-17. These connections are underlined by signatures of positive selection in the disordered N-terminal domain of IL-17E and its cognate receptor, IL-17RB, key modulators of both type 2 immune response and neuronal function, suggesting functional consequences of this understudied domain. Together, our findings suggest that IL-17 biology is repeatedly impacted by lineage-specific selective pressures that dictate both immune and non-immune functions. By anchoring the expanding IL-17 field in an evolutionary framework, we propose a model for understanding the diversification and functional expansion of this and other cytokine families.

evolutionary biology↗

bioRxiv2025

Post-transcriptional Modifications of the Large Ribosome Subunit Assembly Intermediates in E. coli Expressing Helicase-Inactive DbpA Variant

RNA post-transcriptional modifications are ubiquitous across all organisms and serve as fundamental regulators of cellular homeostasis, growth, and stress adaptation. Techniques for the simultaneous detection of multiple RNA modifications in a high-throughput, single-nucleotide-resolution manner are largely absent in the field, and developing such techniques is of paramount importance. We used the Escherichia coli ribosome as a model system to develop novel techniques for RNA post-transcriptional modification detection, leveraging its extensive and diverse array of modifications. For modification detection, we performed reverse transcriptase reactions in the presence of Mn2 and quantified the reverse transcriptase deletions and misincorporations at modification positions using Illumina next-generation sequencing. We simultaneously detected the following modifications in ribosomal RNA (rRNA): 1-methylguanosine (m1G), 2-methylguanosine (m2G), 3-methylpseudouridine, N6,N6-dimethyladenosine, and 3-methyluridine, without chemical treatment. Furthermore, subjecting the rRNA samples to 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate followed by alkaline conditions allowed us to simultaneously detect pseudouridine, 7-methylguanosine (m7G), 5-hydroxycytidine (OH5C), 2-methyladenosine, and dihydrouridine (D). Finally, subjecting the rRNA samples to KMnO4 followed by alkaline conditions allowed us to simultaneously detect m7G, OH5C, and D. Our results reveal that m1G, m2G, m7G, and D are incorporated prior to the accumulation of the 27S, 35S, and 45S large subunit intermediates in cells expressing the helicase-inactive R331A DbpA construct. These intermediates belong to three distinct stages and pathways of large subunit ribosome assembly. Therefore, our results identify the time points in three pathways at which m1G, m2G, m7G, and D are incorporated into the large ribosome subunit and provide a framework for broader studies on RNA modification dynamics.

biochemistry↗

bioRxiv2021

Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis

Amino acid metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an amino acid (AA) transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5-/- and Ndpy/- mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is directly regulated by Wnt/{beta}-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2 (VEGFR2). Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs. Significance StatementAmino acid metabolism in vascular endothelium is important for angiogenesis. SLC38A5 (solute carrier family 38 member 5) is an amino acid (AA) transporter for shuttling neutral AAs such as glutamine across cell membrane. Our work demonstrate that Slc38a5 is highly enriched in retinal vascular endothelium. SLC38A5 regulates endothelial cell glutamine uptake and vascular growth factor receptors to impact blood vessels growth in retinal development and in retinopathies. This work uncovered a novel role of SLC38A5 as a metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in blood vessel endothelium. Findings from this study also suggest that targeting SLC38A5 or relevant AAs can be a new way to protect against retinopathy.

developmental biology↗

bioRxiv2021

SIRT5 is the desuccinylase of LDHA as novel cancer metastatic stimulator in aggressive prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Among patients who developed advanced PCa, 80% suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the details of the mechanisms underlying castration-resistant PCa (CRPC) remains unclear. SIRT5, an NAD+-dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we showed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patients survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase of lysine 118 succinylation (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study investigated the reduction of SIRT5 and LDHA-K118su as a novel mechanism involved in PCa progression. It can also be proposed as a new target that can prevent castration-resistant PCa progression, which is key to PCa treatment.

cancer biology↗