Usp21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of Usp21 dysfunction remain incompletely understood. In this study, we generated Usp21 knockout (KO) mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol (T-CHOL) and free fatty acid (FFA) in Usp21 KO mice compared to wild-type (WT) mice. Next, we performed RNA-sequencing (RNA-seq) to identify genes that Usp21 regulates. The results highlighted several candidate genes based on their biological relevance, and their expression levels were validated by RT-qPCR. The Usp21 KO mice exhibited significant elevations in the expression of the genes Fabp7, Nlrc5, and Ppargc1a, which play an important role in lipid metabolism, compared to WT. These data suggest that Usp21 may play roles in lipid metabolism in association with Fabp7, Nlrc5 and Ppargc1a. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single-nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was significantly associated with hypercholesterolemia. These data suggest that Usp21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

The Mediator complex is a central regulator of eukaryotic transcription, functioning as a dynamic molecular interface between gene-specific transcription factors and RNA polymerase II (Pol II). Although its overall architecture and general role in transcription have been extensively reviewed, accumulating genetic, genomic, and clinical evidence indicates that individual Mediator subunits make distinct and non-redundant contributions to human physiology and disease. In this review, we move beyond a generic description of Mediator function and present a subunit-resolved synthesis of Mediator biology with an emphasis on disease pathogenesis. A key feature of this review is a comprehensive table integrating disease associations and molecular functions of individual human Mediator subunits, enabling rapid assessment of functional specialization across the complex. We further discuss chromatin-based mechanisms of Mediator action, including cooperation with cohesin and architectural factors to regulate enhancer-promoter communication and higher-order genome organization. By organizing recent structural, mechanistic, and pathological findings into a unified framework, this review highlights how disruption of specific Mediator subunits contributes to cancer, developmental disorders, and metabolic disease, and outlines emerging opportunities for therapeutic intervention.

Tick-borne viral infections, including severe fever with thrombocytopenia syndrome virus (SFTSV), are increasingly recognized as a significant threat to global public health owing to their rapid dissemination and high mortality rates. While isolated outbreaks within single species have been documented, reports of multi-host cluster cases remain scarce. This study describes a consecutive, cross-species outbreak of severe fever with thrombocytopenia syndrome disease between April and May 2024 on a remote island in Nagasaki Prefecture that involved four cats and four humans. An interdisciplinary investigation integrating molecular phylogenetic analysis of viral genomes—including previously identified Nagasaki strains of SFTSV—and haplotype network analysis provided insights into the infection dynamics. Despite the absence of confirmed direct contact between cats and humans, four animals and one patient succumbed to the infection. Genomic analyses demonstrated high similarity to circulating Nagasaki strains, whereas haplotype analysis indicated multiple viral introduction events and complex transmission pathways, reflecting diverse sources. These findings underscore the critical need for a One Health approach—integrating human, animal, and vector surveillance—to effectively monitor, understand, and control tick-borne viruses globally, in both endemic and emerging regions.