Working model for the mechanism through which RNA helicase DDX5 inhibits antiviral innate immunity by promoting m6A-methylated antiviral transcripts.

DDX5 was aggregated in the nucleus of virus infected cells, which interacted with METTL3 and regulated the activity of the m6A ‘writer’ complex METTL3/METTL14. Then, the m6A ‘writer’ complex increased m6A modification of DHX58, p65, and IKKγ transcripts and sequentially exported them from nucleus to the cytoplasm, resulting in transcription of DHX58, which was also enhanced while the transcripts IKKγ and p65 were recognized by the m6A reader protein and were degraded in a YTHDF2-dependent manner, which finally resulted in the inhibition ofTBK1 and p65 mediated antiviral pathways.