Title |
RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination
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Published in |
BMC Biology, November 2017
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DOI | 10.1186/s12915-017-0444-9 |
Pubmed ID | |
Authors |
Nila Roy Choudhury, Gregory Heikel, Maryia Trubitsyna, Peter Kubik, Jakub Stanislaw Nowak, Shaun Webb, Sander Granneman, Christos Spanos, Juri Rappsilber, Alfredo Castello, Gracjan Michlewski |
Abstract |
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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 17% |
United States | 1 | 17% |
Germany | 1 | 17% |
Unknown | 3 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 50% |
Scientists | 2 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 144 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 36 | 25% |
Researcher | 25 | 17% |
Student > Bachelor | 18 | 13% |
Student > Master | 17 | 12% |
Student > Postgraduate | 5 | 3% |
Other | 17 | 12% |
Unknown | 26 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 63 | 44% |
Agricultural and Biological Sciences | 24 | 17% |
Immunology and Microbiology | 10 | 7% |
Chemistry | 4 | 3% |
Neuroscience | 3 | 2% |
Other | 7 | 5% |
Unknown | 33 | 23% |