The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function

Yang, Darong; Li, Nan L.; Wei, Dahai; Liu, Baoming; Guo, Fang; Elbahesh, Husni; Zhang, Yunzhi; Zhou, Zhi; Chen, Guo-Yun; Li, Kui

Importantly, the current study significantly advances our understanding of the antiviral mechanism of TRIM56 by showing that TRIM56 is an RNA-binding protein and that its C-terminal region mediates the association with ZIKV RNA in infected cells. In addition, we revealed that host miRNAs are not essential for ZIKV replication and that the restriction of ZIKV by TRIM56 is independent of miRNA biogenesis or its regulation. TRIM56 is currently classified within the subgroup C-V of TRIM proteins [58] , because its C-terminal region was not found to contain a defined protein domain structure. However, we previously found aa 521-748 in the C-terminal portion of TRIM56 constitutes a NHL-like domain that shares homology and conserved residues with the NHL repeat domain of several TRIM-NHL proteins such as TRIM2, TRIM3, and TRIM71 [26] . The NHL repeat domain folds into a sixbladed beta-propeller resembling that of WD40 domains [59] . Part of its surface is positively charged and may potentially interact with nucleic acids, whose backbone is negatively charged.