Selective degradation of plasmid-derived mRNAs by MCPIP1 RNase

Detection and degradation of foreign nucleic acids is an ancient form of host defense. However, the underlying mechanisms are not completely clear. MCPIP1 is an endoribonuclease and an important regulator in both innate and adaptive immunity by targeting inflammatory mRNA degradation. Here we report that MCPIP1 RNase can also selectively detect and degrade the mRNAs encoded by transfected plasmids. In transient transfection, MCPIP1 expression potently degraded the mRNA from exogenously transfected vectors, which is independent on the vector, genes and cell types used. Conversely, the expression of transfected plasmids in MCPIP1-null cells is significantly higher than that in wild-type cells. Interestingly, overexpression of MCPIP1 or MCPIP1 deficiency does not affect the expression of the exogenous genes incorporated into the host genome in a stable cell line or the global gene expression of host genome. This ability is not associated with PKR/RNase L system, as PKR inhibitors does not block MCPIP1-mediated mRNA degradation of exogenously transfected genes. Lastly, expression of MCPIP1 suppressed replication of Zika virus in infected cells. The study may provide a model for understanding the antiviral mechanisms of MCPIP1, and a putative tool to increase the expression of transfected exogenous genes.