Here, we show that SARS-CoV-2 N protein induces the autophagic degradation of two RNAi components (Dicer and XPO5) and two splicing factors (SRSF3 and hnRNPA3), thereby inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Here, HNRNPA3 is linked to pneumonia.