RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination

Choudhury, N. R. et al. (2017) RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC Biology, 15, (doi: 10.1186/s12915-017-0444-9) (PMID:29117863) (PMCID:PMC5678581)

Abstract

Background: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. Results: Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25’s endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. Conclusions: Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Castello, Professor Alfredo
• Authors: Choudhury, N. R., Heikel, G., Trubitsyna, M., Kubik, P., Nowak, J. S., Webb, S., Granneman, S., Spanos, C., Rappsilber, J., Castello, A., and Michlewski, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: BMC Biology
• Publisher: BioMed Central
• ISSN: 1741-7007
• ISSN (Online): 1741-7007
• Copyright Holders: Copyright © 2017 Michlewski et al.
• First Published: First published in BMC Biology 15: 105
• Publisher Policy: Reproduced under a Creative Commons License