Biology subjects

Kunii, N.

Publications and source records attributed to Kunii, N..

2 recordsLinked to original sources

bioRxiv2026

Ribonuclease L Regulates Antiviral Responsiveness through Cleavage of XBP1 mRNA

During viral infection, viral replication perturbs endoplasmic reticulum (ER) homeostasis and triggers the unfolded protein response (UPR). XBP1s, a transcription factor generated by one branch of the UPR, is known to potentiate both innate and adaptive immunity, but its role in antiviral responses remains incompletely understood beyond its ability to augment type I interferon (IFN) mRNA induction. Here, we show that XBP1s positively regulates the RIG-I-like receptors (RLRs), ribonuclease L (RNase L), and protein kinase R (PKR) pathways, indicating that it enhances all three major antiviral response pathways. We further show that RNase L activation rapidly decreases XBP1 mRNA levels in an RNase activity-dependent manner, leading to a prompt reduction in XBP1s expression. Consistent with this, RNase L deletion significantly increased both thapsigargin-mediated XBP1s induction and XBP1s expression following Japan encephalitis virus infection. Poly(I:C)-induced IFNB mRNA expression was significantly enhanced in RNase L-knockout cells. This enhancement was completely abolished by RNase L reconstitution. XBP1 knockdown also significantly attenuated IFNB mRNA expression in RNase L-knockout cells. These findings suggest a negative-feedback loop in which RNase L suppresses XBP1s, thereby fine-tuning antiviral responsiveness during viral infection. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/713401v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@112d312org.highwire.dtl.DTLVardef@df79a9org.highwire.dtl.DTLVardef@1ac571borg.highwire.dtl.DTLVardef@18ac610_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

High-Frequency Activity Encodes the Temporal Dynamics of Hierarchical Prediction Errors in Humans: An Electrocorticography Study

Prediction error refers to the discrepancy between expected and actual sensory input. Its hierarchical organization has been demonstrated through decomposed brain responses in the local-global paradigm, where temporal regularities are established locally at individual stimulus transitions and globally across multi-tone sequence structures. In macaques and marmosets, local and global prediction-error signals have both been found in high-frequency oscillations (60-150 Hz) recorded with ECoG. In humans, however, these signals have primarily been observed in a lower frequency range (30-100 Hz) using EEG. Here, we recorded human ECoG to achieve higher signal fidelity, enabling examination of neural oscillations above 100 Hz (high-frequency activity, HFA), which are believed to be closely linked to local spiking activity. Eight participants listened to auditory sequences that either followed their local and global regularities (local and global standards) or violated them (local and global deviants). Robust HFA responses were observed for the local deviants, but these responses were reduced when the deviants were expected based on the global regularity, indicating both levels of prediction-error processes contribute to the observed activity. Importantly, these HFA responses could be decomposed into two subcomponents: an early component reflecting local prediction-error signals localized to lateral auditory regions, and a late component reflecting global prediction-error signals prominent in both lateral auditory and frontal cortices. Together, these findings demonstrate that neural oscillations above 100 Hz encode hierarchical prediction errors not only in non-human primates but also in humans.

neuroscience↗