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AP News Wire and MSN.com Highlight a Breakthrough Published in Genomic Psychiatry: OTULIN Controls Tau Expression
Within just four days of its 25 November 2025 publication, this Genomic Psychiatry study has captured worldwide media attention: over 40 news outlets in English, Spanish, and Portuguese, including prominent placement on MSN.com and distribution through the Associated Press news wire, whose journalism reaches an estimated 4 billion people daily worldwide.
With ~1.3 billion monthly visits, MSN.com ranks among the world's top news portals. This latest feature continues a remarkable trajectory: more than 20 Genomic Press papers have now appeared on MSN.com, bringing cutting-edge biomedical research to global audiences.
The Discovery
"We originally hypothesized that inhibiting the deubiquitinase OTULIN would promote clearance of toxic tau aggregates by stabilizing linear (M1-linked) ubiquitin chains," said first author Dr. Karthikeyan Tangavelou. "Instead, the results completely overturned our expectations."
Working with patient-derived neurons (iPSNs) carrying sporadic Alzheimer's pathology and human SH-SY5Y neuroblastoma cells, the team led by Dr. Kiran Bhaskar (University of New Mexico) and Dr. Francesca-Fang Liao (University of Tennessee) discovered that OTULIN, previously known only for controlling inflammation, plays a previously unrecognized central role in neuronal RNA metabolism and directly regulates expression of the tau protein (encoded by the MAPT gene).
Key findings:
- Patient-derived Alzheimer's neurons showed elevated OTULIN protein and increased pathogenic phospho-tau (AT8+, AT180+, PHF-1+).
- A novel small-molecule inhibitor of OTULIN (UC495) significantly reduced pathogenic phospho-tau species in these human neurons.
- Complete genetic knockout of OTULIN eliminated tau expression entirely, not only the protein, but also MAPT mRNA, while leaving neuronal survival and differentiation intact.
- RNA-sequencing revealed massive transcriptome remodeling (>13,000 genes and >44,000 RNA transcripts differentially expressed), confirming OTULIN as a master regulator of RNA processing, stability, and gene expression in neurons.
These results, published in Genomic Psychiatry (2025), reveal an unexpected non-canonical function of OTULIN and identify it as a promising new therapeutic target for Alzheimer's disease and other tauopathies.
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