Biology subjects

Mason, N.

Publications and source records attributed to Mason, N..

3 recordsLinked to original sources

bioRxiv2026

The nuclear Argonaute HRDE-1 broadly interacts with euchromatin via an RGG domain to enable transgenerational epigenetic silencing

Small RNA(sRNA)-guided transcriptional repression, a process termed as nuclear RNAi, safeguards genome integrity and germline development. Central to this pathway are the highly conserved Argonaute (AGO) proteins, which are guided by sRNAs to mediate transcriptional silencing and heterochromatin formation at the target locus. The mechanism of how nuclear AGO proteins engage chromatin remains poorly understood. By studying C. elegans nuclear AGO HRDE-1, we found that an intrinsically disordered arginine-glycine-glycine (RGG) domain in HRDE-1 is essential for siRNA-guided transgenerational epigenetic silencing and germline immortality. The function of RGG occurs in the downstream of siRNA loading and nuclear localization. Mutant HRDE-1 that lacks the RGG domain is defective in binding to the chromatin of the siRNA targets. Strikingly, ChIP-seq analysis reveals that HRDE-1 interacts with hundreds of highly transcribed euchromatic protein-coding genes in the germ cells, which is unexpected for an epigenetic silencing protein. The HRDE-1-euchromatin interaction is not mediated by siRNAs but requires the RGG domain. The interaction appears to be necessary but not sufficient to cause gene silencing. We propose that the initial siRNA-independent, RGG-dependent HRDE-1-chromatin interaction enables HRDE-1 to enter the transcribing chromatin compartment, a likely prerequisite for the subsequent siRNA-pre-mRNA interaction. Given the prevalence of the RGG domain in eukaryotic proteins, we constructed chimera HRDE-1 proteins and found that RGGs from other proteins, including human hnRNP U, can substitute for the HRDE-1 RGG to restore chromatin binding and transgenerational silencing. Our findings suggest an evolutionarily conserved role for RGG-rich intrinsically disordered regions in coupling AGOs and other RNA-binding proteins to active chromatin as a mechanism to target nascent pre-mRNA.

molecular biology↗

bioRxiv2026

Tuning in together: LSD enhances inter-brain synchrony and felt connectedness in romantic couples

Social connection is fundamental to human wellbeing. Serotonergic psychedelics such as lysergic acid diethylamide (LSD) acutely heighten subjective connectedness, yet their effects on real-time social connection remain poorly understood. Using EEG hyperscanning in a randomized, double-blind, placebo-controlled crossover study, we recorded neural activity simultaneously from both members of healthy romantic couples (N=25) who received LSD (50 g) or placebo together, across resting and interactive states. LSD increased subjective connectedness, including feelings of love, closeness, trust, and being "in sync," while reducing loneliness, compared to placebo. This affiliative shift dissociated from the drugs pharmacokinetic time-course, remaining elevated as subjective intensity and plasma concentration declined. In parallel, LSD increased inter-brain synchrony during shared rest, carried specifically by theta-band amplitude-envelope coupling. Importantly, this effect survived two complementary controls. First, it exceeded coupling between unrelated individuals and second the effects depended on contemporaneous neural alignment rather than shared drug-induced dynamics. Exploratory analyses showed that romantic partners with greater resting synchrony reported greater feelings of connectedness. These findings provide the first evidence that a psychedelic enhances brain-to-brain coupling between people, linking a pharmacologically induced state of felt connection to a measurable signature shared across interacting brains.

neuroscience↗

bioRxiv2023

The unique neural signature of your trip: Functional connectome fingerprints of subjective psilocybin experience

The emerging neuroscientific frontier of brain fingerprinting has recently established that human functional connectomes (FCs) exhibit fingerprint-like idiosyncratic features, which map onto heterogeneously distributed behavioural traits. Here, we harness brain-fingerprinting tools to extract FC features that predict subjective drug experience induced by the psychedelic psilocybin. Specifically, in neuroimaging data of healthy volunteers under the acute influence of psilocybin or a placebo, we show that, post psilocybin administration, FCs become more idiosyncratic due to greater inter-subject dissimilarity. Moreover, whereas in placebo subjects idiosyncratic features are primarily found in the frontoparietal network, in psilocybin subjects they concentrate in the default-mode network (DMN). Crucially, isolating the latter revealed an FC pattern that predicts subjective psilocybin experience and is characterised by reduced within-DMN and DMN-limbic connectivity, as well as increased connectivity between the DMN and attentional systems. Overall, these results contribute to bridging the gap between psilocybin-mediated effects on brain and behaviour, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging. Author summaryThe trending field of brain fingerprinting focuses on characterising fingerprint-like idiosyncratic features of human functional connectomes (FCs), which have been shown to predict heterogeneously distributed behavioural traits. Here, we apply brain-fingerprinting methods to fMRI data from subjects who were administered the psychedelic psilocybin or a placebo. We find that, compared to the placebo condition, subjects under acute psilocybin effects exhibited more idiosyncratic FCs, with idiosyncratic features being largely concentrated in the default-mode network (DMN). Furthermore, we isolated an idiosyncratic FC pattern that predicted reports of subjective psilocybin experiences. This pattern was characterised by altered DMN connectivity, specifically by reduced within-DMN and DMN-limbic connectivity, and increased connectivity between the DMN and attentional systems. This work paves the way for exciting new research harnessing pharmacological brain fingerprinting.

neuroscience↗