News & Views

The interface between biomolecular condensates and cellular membranes underlies many biological processes, yet how biomolecules and lipids reciprocally influence one another’s phase behavior remains poorly understood. A study now shows that membrane composition modulates biomolecular condensation on the membrane, pointing to a new regulatory mechanism of condensation in cells.

Thymine DNA-glycosylase (TDG) has established roles in DNA repair, methylation and transcription, with some implications for cancer development. A study has now identified a synthetic lethality between TDG and p53 in cancer cells, caused by the accumulation of double-stranded RNA.

Ideal efficacy photoswitching is introduced as a concept in controlling protein activity with light. Largely independent of the concentration of a light-responsive compound, it enables TRPC4 and TRPC5 channels to be precisely agonized or antagonized depending on the color of light used.

Although inhibiting epigenetic enzymes holds strong therapeutic promise, off-target effects remain a prevailing challenge. This study instead targets an accessory reader to fine-tune the inhibitory pathway.

An innovative method to identify ligands for orphan G protein-coupled receptors has been developed using site-specific UV-mediated crosslinking. With this approach, the neuropeptide Little-LEN was identified as an agonist for GPR50, which together regulate energy expenditure in response to metabolic state.

PCMT1, long known for its role in protein repair, can also install C-terminal degrons recognized by cereblon (CRBN). This finding links protein repair and degradation through shared chemistry, identifying an enzymatic writer of a C-terminal degradation mark with translational potential.

The function of membrane proteins is dependent on the lipid environment, but whether this is due to high-affinity, ligand-like linkage is unclear. Extensive molecular dynamics simulations and single-molecule FRET measurements now show that the dimerization of a chloride transporter is instead controlled by a preferential solvation mechanism.

A recent study developed a refined photocatalytic labeling-based method to capture and sequence physically interacting cells in situ and discovered how tumors induce pro-tumor neutrophils via cell contact.

Molecular glue degraders induce or stabilize interactions between E3 ligases and target proteins. Beyond compound-induced, direct interactions, researchers recently uncovered an allosteric mechanism whereby a drug alters the target protein’s conformation, enabling high-affinity neo-binding to an E3 ligase and triggering degradation.

How biogenic crystals form within cells despite their building blocks being water insoluble is a conundrum. Now, it has been shown that zebrafish control the crystallization process by modulating organellar pH: first to accumulate guanine, and then to crystallize it.

Research shows how small nuclear RNAs act as a cellular GPS to guide endogenous RNA-modifying enzymes to their targets for site-specific RNA editing. This approach boosts efficiency and safety when editing high-complexity genes, broadening the therapeutic potential.

The construction and assembly of information-processing biomaterials are limited by the need for laborious assembly of various circuits. A new framework to assemble protein-based elements encoding complex Boolean operations enables user-defined release of biomolecules from these materials.

mRNA has emerged as an important class of therapeutic molecules. Now, an artificial intelligence (AI)-driven framework, which can design mRNA sequences with enhanced stability and translational efficiency, has been reported. This method for designing mRNA sequences is known as ‘generative models for RNA’ (GEMORNA) and could help to design more effective mRNA-based treatments.

Approaches to study lipid composition with leaflet-specific resolution in living cells have been lacking. A new method — fluorogen-activating coincidence encounter sensing (FACES) — combines biorthogonal metabolic labeling with organelle-targeted fluorogen-activating proteins to selectively visualize lipids on leaflets of interest in any organelle.

Directed evolution is typically a slow and labor-intensive process that relies on multiple cycles of mutation to accelerate the development of desired protein traits. Now, a platform, named T7-ORACLE, has been developed that enables fast and scalable protein evolution.

Pharmacological targeting of missense TP53 mutations has traditionally failed owing to the mutant heterogeneity, gain-of-function oncogenic properties and paradoxical stability of mutant p53 protein. A ‘p53-conditional’ proximity strategy promises to eradicate TP53 missense mutant-driven cancer by exploiting its abundance.

A study establishes intrinsically disordered regions (IDRs) as a new module in chimeric antigen receptor (CAR) engineering. The intrinsic biophysics of IDRs — transient, multivalent interactions — can be exploited to optimize CAR T cell therapies via enhanced clustering and synapse formation where conventional approaches fall short.

New work reveals how acetylation of the Mediator subunit MED1 tunes transcriptional condensates and RNA polymerase II pausing during stress responses, highlighting a post-translational switch that connects phase behavior to gene activation in cellular stress resilience.

Hydrogen peroxide (H₂O₂) is a key signaling molecule involved in many processes that affect health and contribute to disease, but tracking its real-time dynamics inside living cells remains challenging. A new set of biosensors now enables accurate, multiparametric monitoring of H₂O₂ levels without interference from changes in pH or oxygen.

A matching pseudouridine in premature termination codons and in the anticodons of cognate tRNAs promotes ribosome readthrough and avoids nonsense-mediated mRNA decay.