Splicing suppression alters the STING transcription start site to attenuate antiviral innate immunity.

September 29, 2026| Source: Proceedings of the National Academy of Sciences of the United States of America

The cGAS (cyclic GMP-AMP synthase)-STING (Stimulator of interferon genes) pathway plays a central role in antiviral innate immunity in vertebrates. Recent studies have shown that invertebrates possess a related cGLR (cGAS-like receptor)-STING pathway. However, due to the lack of direct evidence demonstrating viral evasion of cGLR-STING-mediated immunity, the functional importance of cGLR-STING pathway in antiviral responses remains uncertain in invertebrates. Here, we show that an insect picorna-like virus CrPV (Cricket Paralysis virus) inhibits STING-mediated antiviral activity by altering the transcription start site of STING . Mechanistically, CrPV infection down-regulates several spliceosomal genes and disrupts pre-mRNA splicing. This splicing impairment is sufficient to stall RNA polymerase II in transcriptional initiation condensates, reduce global transcription efficiency, and reprogram the transcription start site of STING . Such a shift diverts STING expression from a functional antiviral isoform to a nonantiviral variant that partially suppresses STING activity, thereby disabling the cGLR-STING pathway. Our findings uncover an unconventional viral immune evasion strategy and an unexpected link between splicing suppression and STING-mediated antiviral response. Given the evolutionary conservation of splicing mechanisms and STING-like pathways, this mechanism may represent a broadly applicable regulatory principle in immune defense across species.

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Extensive glacier loss in the coterminous United States.

Glaciers populate the mountain ranges of the western conterminous United States and despite their importance to alpine hydrology, their area and volume change have never been comprehensively evaluated. Our study shows that since the mid-twentieth century about one-quarter of the glaciers have disappeared and the overall area and volume are reduced by one-third. The pattern of glacier shrinkage suggests most glaciers in the conterminous United States are largely maintained by local topographic in

Physical/TechOctober 20, 2026

Reaction-based cryo-EM resolves the continuous conformational spectrum of CTP synthase catalysis.

Capturing enzymes under native turnover conditions remains a grand challenge in structural biology. Here, we develop a reaction-based cryo-electron microscopy (cryo-EM) strategy that directly samples Drosophila melanogaster cytidine triphosphate synthase (CTPS) from actively catalyzing mixtures containing only natural substrates and allosteric effectors. By integrating reaction-based sampling with three-dimensional variability analysis, we resolve a continuous conformational spectrum of CTPS dur

Physical/TechOctober 20, 2026

GTP orchestrates CTP synthase via an allosteric effector-cycling mechanism.

Cytidine triphosphate (CTP), a fundamental building block of RNA, plays vital roles in diverse biological processes. CTP synthase (CTPS) is the only known enzyme for de novo synthesis of CTP. Efficient CTPS catalysis requires guanosine triphosphate (GTP) in a dose-dependent, nonconsumptive manner; however, the precise mechanism by which GTP drives CTP formation remains unclear. Here, we integrate a series of cryo-EM structures of Drosophila melanogaster CTPS captured from actively catalyzing sam

Physical/TechOctober 20, 2026

Antiferromagnetism and tightly bound Cooper pairs induced by kinetic frustration.

Antiferromagnetism and superconductivity are often viewed as competing orders in correlated electron systems. Here, we demonstrate that kinetic frustration in hole motion facilitates their coexistence within the square-lattice repulsive Hubbard model. Combining exact analytical solutions on tailored geometries with large-scale numerical simulations, we reveal a robust pairing mechanism: Holes on opposite sublattices behave as if they carry opposite effective charges due to spin singlet formation

Physical/TechOctober 20, 2026

Coordinated transformations of the labyrinth and occiput during the dinosaur-bird transition.

Evolutionary shape changes of the vertebrate semicircular canals (SCCs) are often ascribed to evolutionary transitions in locomotion, including the origin of flight during the dinosaur-bird transition. However, the potential for transformations of braincase architecture to influence SCC shape independent of sensory-functional adaptation has generally been overlooked. We evaluate the influence of both factors using a large dataset of 146 living and recently extinct crown birds, including taxa rep