Journal
BMC BIOLOGY
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12915-017-0444-9
Keywords
Novel RNA-binding proteins; TRIM25; ZAP; RNA-binding domain; PRY/SPRY
Categories
Funding
- Wellcome Trust [105246, 084229, 096996, 091549, 091020]
- MRC [G10000564, MR/K001744/1]
- Wellcome Trust Centre Core Grants [077707, 092076]
- NERC [R8/H10/56]
- BBSRC [BB/J004243/1]
- Wellcome Trust [103139/Z/13/Z] Funding Source: Wellcome Trust
- Biotechnology and Biological Sciences Research Council [BBS/E/D/20310000] Funding Source: researchfish
- Medical Research Council [G1000564, MR/K001744/1] Funding Source: researchfish
- Wellcome Trust [103139/Z/13/Z] Funding Source: researchfish
- BBSRC [BBS/E/D/20310000] Funding Source: UKRI
- MRC [MR/K001744/1, G1000564, MC_UU_12014/10, MR/L019434/1] Funding Source: UKRI
Ask authors/readers for more resources
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 RNArelated 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available