hnRNP K pathology in neurodegenerative diseases
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are essential RNA-binding proteins involved in regulating nucleic acid metabolism. Among them, hnRNP K stands out for its versatility. While the pathological redistribution of hnRNP K to the cytoplasm has been linked to various malignancies, its role in neurodegenerative diseases has remained largely unexplored. We unveiled hnRNP K mislocalisation in pyramidal neurons of the frontal cortex as a novel neuropathological hallmark associated with frontotemporal lobar degeneration (FTLD) and ageing. Notably, this mislocalisation is mutually exclusive with TDP-43 and tau inclusions and does not colocalise with mitochondrial, autophagosomal, or stress granule markers. Furthermore, we demonstrate that silencing hnRNP K in neuronal cells leads to significant transcriptomic alterations, including the induction novel cryptic exon events. These findings were validated in both hnRNP K knockdown models and FTLD brain tissues with hnRNP K nuclear depletion. Our results provide compelling evidence that hnRNP K mislocalisation contributes to diseas by driving widespread splicing changes, offering new insights into the molecular mechanisms underlying these devastating disease.
Date: 29 November 2024, 13:00
Venue: Sherrington Library, off Parks Road OX1 3PT
Venue Details: Sherrington Building
Speaker: Professor Tammaryn Lashley (University College London)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organisers: Dr Mootaz Salman (DPAG, University of Oxford), Associate Professor Samira Lakhal-Littleton (DPAG, University of Oxford)
Organiser contact email address: events@dpag.ox.ac.uk
Host: Dr Mootaz Salman (DPAG, University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Hannah Simm