TRIM25, an RNA-binding E3-ubiquitin ligase, plays a crucial role in the innate immune response against RNA viruses, yet the specifics of its mechanism remain unclear.

Preliminary data suggest that TRIM25’s impaired functions reduce antiviral activity, but the molecular details are unknown. This project aims to dissect the relationship between TRIM25’s RNA-binding, its E3-ligase activity, and antiviral efficacy. Employing a comprehensive approach, including protein proximity assays, genome-wide RNA binding analysis, and structural biology, the study seeks to identify TRIM25’s ubiquitylation and RNA targets before and after viral infection. Additionally, experiments with various RNA viruses will determine if TRIM25’s defence mechanism is specific to Sindbis virus or applicable across different viral families. This collaborative effort will advance our understanding of TRIM25’s role in infection biology.

Janosch Hennig (EMBL), Mikhail Savitski (EMBL), Sagar Bhogaraju (EMBL), Alfredo Castello Palomares (CVR Glasgow)

Exploring the expanding universe of host-virus interactions mediated by viral RNA
Castello A, Álvarez L, Kamel W, Iselin L, Hennig J
Molecular Cell, Volume 84, Issue 19, 3706 – 3721 (2024)
doi:10.1016/j.molcel.2024.08.027

The molecular dissection of TRIM25’s RNA-binding mechanism provides key insights into its antiviral activity
Álvarez L, […], Castello A, Hennig J
Nature Communications, Volume 15, Article number: 8485 (2024)
doi:10.1038/s41467-024-52918-x