Biology subjects

Park, C.-G.

Publications and source records attributed to Park, C.-G..

4 recordsLinked to original sources

bioRxiv2026

ADAR-Sense: an open-access, species-agnostic web tool for automated, user-customisable ADAR-based RNA sensor design

BackgroundEngineered synthetic RNAs enable cellular control by sensing and responding to intracellular biomolecules. Recently developed sense-edit-switch RNAs (sesRNAs) based on Adenosine Deaminase Acting on RNA (ADAR)--which edits a stop codon to switch on custom payload translation in the presence of a target RNA--are consistently functional across different species. The ability of sesRNAs to couple bespoke payload translation to the presence of cell type-specific transcripts will usher in an era of precise cell-targeted biotechnological interventions. ResultsTo expedite the generation of sesRNAs, we develop ADAR-Sense--a universal web tool for automated sensor design based on user-defined sensor length, sensor-target RNA mismatch number, mismatch proximity to the ADAR-editable stop codon, and targeted custom element inclusion for improved ADAR recruitment and subsequent payload induction. ConclusionsCompared to current tools, the simplicity and flexibility of ADAR-Sense will streamline the design and screening of sesRNAs in new cell types and conditions, supporting the swift adoption of this sensing platform in both basic and translational research.

synthetic biology↗

bioRxiv2025

Structural Basis of Cold and Menthol Sensing by TRPM8

The transient receptor potential melastatin member 8 (TRPM8) is a polymodal ion channel that senses cold and menthol in mammals. Despite prior structural studies, the mechanisms by which cold and menthol activate TRPM8 remain unresolved. Here, we present cryo-EM structures representing the cold and menthol-dependent activation trajectories, combined with extensive functional analyses. We captured snapshots of cooling-dependent pore opening, which involves dramatic pore rearrangement, suggesting a mechanism for cold sensing. Moreover, menthol binds dynamically to induce channel activation, which may underlie menthol specificity for TRPM8. Finally, we show how TRPM8 integrates multiple modalities (cold and menthol) through overlapping but non-identical pathways, revealing the temperature-specific "cold spot". These findings enhance our understanding of the molecular basis of physically and chemically induced cool sensation in mammals.

biophysics↗

bioRxiv2025

Proteome-wide computational analyses reveal links between protein condensate formation and RNA biology

Biomolecular condensates mediate dynamic compartmentalization of cellular processes. The multivalent interactions that underlie biomolecular condensation are often promoted by intrinsically disordered regions (IDRs) within proteins. While the role of IDRs in biomolecular condensates is well appreciated, predicting whether an IDR forms condensates in cells remains challenging. Here, we developed a machine learning model to predict condensation behavior of IDRs, analyzing 215 IDRs from fusion oncoproteins in HEK293T cells. Our study identified distinct sequence-derived physicochemical features associated with condensation. Leveraging these data, our model predicts that [~]12% of the [~]13,000 IDRs in the human proteome are likely to form cellular condensates. Proteins with condensate-forming IDRs are enriched in functions involving RNA-related processes and membrane-less organelles (MLOs), highlighting their role in MLO assembly and function. Our model, available via the SAK3.0 web server (https://sak.stjude.org), provides a powerful resource for studying IDR-driven phase separation across proteomes, offering insights into biomolecular condensates and their biological roles.

bioinformatics↗

bioRxiv2025

Granular component sub-phases direct ribosome biogenesis in the nucleolus

The hierarchical, multiphase organization of the nucleolus underlies ribosome biogenesis. Ribonucleoprotein particles that regulate ribosomal subunit assembly are heterogeneously disposed in the granular component (GC) of the nucleolus. However, the molecular origins of the GCs spatial heterogeneity and its association with ribosomal subunit assembly remain poorly understood. Here, using super-resolution microscopy, we uncover that key GC biomolecules, including nucleophosmin (NPM1), surfeit locus protein 6 (SURF6), and ribosomal RNA (rRNA), are heterogeneously localized within sub-phases in the GC. In vitro reconstitution showed that these GC biomolecules form multiphase condensates with SURF6/rRNA-rich core and NPM1-rich shell, providing a mechanistic basis for GCs spatial heterogeneity. SURF6s association with rRNA is weakened upon ribosome subunit assembly, enabling NPM1 to extract assembled subunits from condensates--suggesting an assembly-line-like mechanism of subunit efflux from the GC. Our results establish a framework for understanding the heterogeneous structure of the GC and reveal how its distinct sub-phases facilitate ribosome subunit assembly.

biochemistry↗