Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117, Heidelberg, Germany.
Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, UK.
Nat Commun. 2024 Oct 1;15(1):8485. doi: 10.1038/s41467-024-52918-x.
TRIM25 is an RNA-binding ubiquitin E3 ligase with central but poorly understood roles in the innate immune response to RNA viruses. The link between TRIM25's RNA binding and its role in innate immunity has not been established. Thus, we utilized a multitude of biophysical techniques to identify key RNA-binding residues of TRIM25 and developed an RNA-binding deficient mutant (TRIM25-m9). Using iCLIP2 in virus-infected and uninfected cells, we identified TRIM25's RNA sequence and structure specificity, that it binds specifically to viral RNA, and that the interaction with RNA is critical for its antiviral activity.
TRIM25 是一种 RNA 结合泛素 E3 连接酶，在 RNA 病毒的先天免疫反应中具有核心但理解甚少的作用。TRIM25 的 RNA 结合与其在先天免疫中的作用之间的联系尚未确定。因此，我们利用多种生物物理技术鉴定了 TRIM25 的关键 RNA 结合残基，并开发了一种 RNA 结合缺陷突变体 (TRIM25-m9)。使用 iCLIP2 在感染和未感染病毒的细胞中，我们确定了 TRIM25 的 RNA 序列和结构特异性，它特异性地结合病毒 RNA，并且与 RNA 的相互作用对于其抗病毒活性至关重要。
