Three-dimensional (3D) genome organization plays a central role in gene regulation, chromatin folding, and genome stability. Although chromosome-conformation capture (3C)-derived methods have revolutionized our understanding of genome architecture, most remain limited in resolution, in their capacity to detect multiway interactions and in their ability to distinguish sister chromatids. Here, we present CAD-C, a new chromatin-conformation […]
5′ RNA Aminoacylation via Interstrand Acyl-Transfer
The catalytic transformations driving coded protein synthesis revolve around linkage of amino acids to molecules of RNA as 2’/3′-aminoacyl esters. This defining molecular species of life is installed, supervised and utilised by complex catalysts, but its relative hydrolytic lability limits its accumulation and behaviour during the early development of the translation system in a simpler […]
Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction
Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that regulates diverse cytosolic acetylation through its two catalytic deacetylase domains and a C-terminal zinc finger ubiquitin-binding domain (ZnF-UBD) which mediates key protein-protein interactions (PPIs) that couple deacetylation and ubiquitin-dependent degradation. While most HDAC6 inhibitors target the catalytic domains, the ZnF-UBD represents an underexplored target. […]
Molecular basis for thermoresponsive protein condensation in plants
Plants continuously experience temperature fluctuations that shape their physiology, development, and survival. Yet, how plants sense and adapt to elevated temperatures at the molecular level remains only partially understood. Here, we uncover a sequence-encoded mechanism by which plant proteins directly sense temperature through phase separation. Focusing on prion-like low-complexity domains (PLCDs) in Arabidopsis thaliana, we […]
Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction
Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that regulates diverse cytosolic acetylation through its two catalytic deacetylase domains and a C-terminal zinc finger ubiquitin-binding domain (ZnF-UBD) which mediates key protein-protein interactions (PPIs) that couple deacetylation and ubiquitin-dependent degradation. While most HDAC6 inhibitors target the catalytic domains, the ZnF-UBD represents an underexplored target. […]
5′ RNA Aminoacylation via Interstrand Acyl-Transfer
The catalytic transformations driving coded protein synthesis revolve around linkage of amino acids to molecules of RNA as 2’/3′-aminoacyl esters. This defining molecular species of life is installed, supervised and utilised by complex catalysts, but its relative hydrolytic lability limits its accumulation and behaviour during the early development of the translation system in a simpler […]
Molecular basis for thermoresponsive protein condensation in plants
Plants continuously experience temperature fluctuations that shape their physiology, development, and survival. Yet, how plants sense and adapt to elevated temperatures at the molecular level remains only partially understood. Here, we uncover a sequence-encoded mechanism by which plant proteins directly sense temperature through phase separation. Focusing on prion-like low-complexity domains (PLCDs) in Arabidopsis thaliana, we […]
CAD-C reveals centromere pairing and near-perfect alignment of sister chromatids
Three-dimensional (3D) genome organization plays a central role in gene regulation, chromatin folding, and genome stability. Although chromosome-conformation capture (3C)-derived methods have revolutionized our understanding of genome architecture, most remain limited in resolution, in their capacity to detect multiway interactions and in their ability to distinguish sister chromatids. Here, we present CAD-C, a new chromatin-conformation […]
DGAT1-dependent lipid droplet synthesis in microglia attenuates neuroinflammatory responses to lipopolysaccharides.
Lipid droplets (LD) are dynamic storage organelles for triglycerides (TG). LD act as a hub that modulates the availability of fatty acids to sustain metabolic needs and the generation of fatty-acid derived signals. Recent evidence demonstrates that LD metabolism regulates immune responses including in microglia, the resident immune cells of the central nervous system. We […]
Helix: a structure-aware deep learning model for accurate prediction of A-to-I RNA editing by endogenous ADARs
Adenosine deaminase acting on RNA (ADAR) converts adenosine to inosine within double-stranded RNA (dsRNA) and can be co-opted for therapeutic RNA editing by introducing dsRNA substrates in trans using programmable guide RNAs (gRNAs). However, ADAR’s natural promiscuity necessitates sophisticated gRNA designs to achieve efficient and specific editing. Here we present Helix, a predictive model that […]