Structural insights into spectral tuning and retinal exchange in cone visual pigments

Researchers investigated how red and green cone pigments in primates achieve their distinct light sensitivities despite sharing the same chromophore and differing at only a handful of amino acid residues. Using cryo-electron microscopy structures of macaque red and green cone pigments, combined with low-temperature vibrational spectroscopy and quantum mechanical/molecular mechanical modeling, they found that a single residue — threonine 285 — drives most of the spectral difference between the two pigments by altering chromophore electrostatics through its hydroxyl dipole, with steric contributions playing a smaller role. The structures also revealed lateral, membrane-facing openings in cone pigments that are absent in inactive rhodopsin. Comparisons with active-state structures and mutational experiments suggest these openings are gated by activation and facilitate retinal exchange, helping explain how cone pigments regenerate much faster than rod pigments — a property important for sustained color vision in bright-light conditions.

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Single-cell multiomics of neuron activation reveals context-specific genetics of brain disorders

Identifying the causal genetic variants underlying neuropsychiatric disorders has proven difficult partly because those variants may only exert their effects in specific biological contexts—such as when neurons are actively firing—that are hard to study at scale in living humans. To address this, researchers profiled gene expression and chromatin accessibility simultaneously at the single-nucleus level in neurons derived from induced pluripotent stem cells representing 100 donors, comparing resting and stimulated states. They discovered numerous genetic variants that influence gene activity and chromatin openness specifically during neuronal activation, with the chromatin-accessibility changes accounting for a notable share of neuropsychiatric disease heritability. Combining these data with genome-wide association study results uncovered risk variants and genes—including those tied to cholesterol metabolism—whose relevance to disorders like schizophrenia or bipolar disorder was only detectable after stimulation. The findings underscore how studying neurons in an activated state can unmask otherwise hidden genetic contributions to brain disease.

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Lariat RNA debranching prevents harmful siRNA burst in plants

During pre-mRNA splicing, introns are released as lariat-shaped RNA structures that are normally broken down by the debranching enzyme DBR1. Loss of DBR1 causes developmental arrest, but the reason has been poorly understood. Researchers discovered that when lariat RNAs accumulate — either due to DBR1 loss or pathogen infection — they are processed by RNA-dependent RNA polymerases and Dicer-like proteins into 21- and 22-nucleotide small interfering RNAs (called lasiRNAs). This triggers a broader burst of siRNAs derived from exonic sequences, which interferes with gene expression. Notably, these siRNAs preferentially target immunity-related genes, undermining plant defense. The findings reframe DBR1-mediated lariat degradation not merely as routine RNA housekeeping but as a safeguard that prevents inappropriate activation of the plant's RNA silencing machinery — protecting both normal development and the integrity of immune responses.

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