In this issue of Molecular Cell, Schärfen et al.1 describe an advanced RNA structure-probing technology called CoSTseq that enables transcriptome-wide detection of nascent RNA base pairing during transcription in living yeast cells.

In this issue, Guo et al.1 and Chen et al.2 resolved the cryo-EM structures of G protein-coupled receptor (GPR) 4 and GPR68, unveiling that histidine protonation initiates conformational rearrangements and dictates G protein coupling bias, illuminating pH-sensing mechanisms.

In a recent issue of Molecular Cell, Genoyer et al.1 show that during West Nile virus infection, escaped, cytoplasmic, anti-genomic negative-sense viral RNA triggers an antiviral response via RIG-I activation. Flaviviruses typically hide −vRNA in replication compartments to avoid detection, but some −vRNA leaks, possibly aided by viral capsid proteins.

Recent elegant studies in Nature1,2 uncovered an unprecedented molecular glue-like mechanism of action for the preclinical drug UM171. This small molecule showed striking functional and structural similarities to brain cancer mutations that prompt neomorphic protein interactions. This phenomenon of chemical-genetic convergence could be reverse-engineered to aid the rational design of induced proximity

Mitochondria serve as central hubs in cellular metabolism by sensing, integrating, and responding to metabolic demands. This integrative function is achieved through inter-organellar communication, involving the exchange of metabolites, lipids, and signaling molecules. The functional diversity of metabolite exchange and pathway interactions is enabled by compartmentalization within organelle membranes

In this issue, Huang et al.1 report the acetylation of METTL3 as a negative regulator of m6A deposition of chromatin-associated regulatory RNAs from enhancers and promoters. This acetylation is mediated by p300 and positively regulated by PAK2.

In this issue of Molecular Cell, Tang et al.1 demonstrate that the ketone body β-hydroxybutyrate (BHB) promotes the biogenesis of mitochondrial-derived vesicles (MDVs) via lysine β-hydroxybutyrylation (Kbhb) on SNX9, revealing a way to fine-tune the mitochondrial quality control pathway with metabolites.

In this issue of Molecular Cell, Kiss et al.1 introduce UbiREAD, a technology that deciphers ubiquitin chain-mediated degradation in living cells, revealing a hierarchy where K48 chains of at least three ubiquitins drive rapid proteasomal degradation and branched K48/K63 chains follow substrate-anchored rules.

Cancer cells subvert the immune system by reprogramming their metabolism. In a recent study in Nature, Ikeda et al.1 show how cancer cells can directly transfer mitophagy-resistant mitochondria to tumor-infiltrating lymphocytes, promoting their homoplasmic replacement and undermining cancer immunity.

Enzyme design has struggled to emulate the complexity and catalytic proficiency of natural enzymes. Lauko et al.1 show that with the help of deep learning, the design of serine hydrolases that rival nature’s ingenuity is possible.

Pathogenic or symbiotic bacteria residing inside eukaryotic cells often foil attempts to eliminate them by secreting deubiquitinases into the host. In this issue of Molecular Cell, Hermanns et al.1 uncover an unexpected “clippase” activity in certain bacterial deubiquitinases, which cleaves substrate-linked ubiquitin within the ubiquitin C terminus, thereby inactivating it.

A recent study in Molecular Cell by Ogawa et al.1 demonstrates that the protein SLFN11, which is a potent biomarker for sensitivity to DNA damage, induces p53-independent apoptosis through inhibition of protein translation.

In a recent issue of Molecular Cell, Fesenko et al.1 report a systematic investigation of intergenic regions within Enterobacteriaceae, shedding light on a vast, unexplored microprotein landscape that has been overlooked in well-characterized bacterial genomes.

In this issue of Molecular Cell, Schmid and Walter present “Predictomes,”1 a machine-learning-based platform that utilizes AlphaFold-Multimer (AF-M) to identify high-confidence protein-protein interactions (PPIs). Their SPOC classifier is better than existing methods at separating true and false interactions.

In a recent Cell study, Yirmiya et al.,1 using AlphaFold2-Multimer co-folding analyses, identify multiple phage inhibitors of bacterial defense systems on a proteome-wide scale and uncover a novel inhibition mechanism of these anti-defense proteins. The study significantly promotes our understanding of phage-bacteria interactions.

The recently discovered lysine lactylation represents a critical post-translational modification with widespread implications in epigenetics and cancer biology. Initially identified on histones, lysine lactylation has been also described on non-histone proteins, playing a pivotal role in transcriptional activation, protein function, and cellular processes. Two major sources of the lactyl moiety have

(Molecular Cell 84, 476–489.e1–e10; February 1, 2024)

In this issue of Molecular Cell, Shi et al.1 elucidate a novel role of host factor ZCCHC3 in positively regulating RLR and cGAS signaling through the binding of nucleic acids and induction of liquid phase condensation.

In a recent article in Nature, Nobori et al.1 unveil spatiotemporal dynamics of immune states of plant cells during pathogen infection. Cells in contact with the pathogen act as primary immune responders (PRIMER) and propagate immune responses to mount effective defenses.

(Molecular Cell 84, 2822–2837.e1–e11; August 8, 2024)