Fig. 1. Landscape of m⁶A methylome in positive-sense genomic RNA of SARS-CoV-2.

a Vero cells were infected with SARS-CoV-2. Supernatant was harvested 6, 24, 56 h later for quantification of SARS-CoV-2 RNA by qRT-PCR. n = 3. b Representative fields of SARS-CoV-2-infected Vero cells (S protein, green) and nuclei (DAPI, blue) at different time points including 6, 24 and 56 hpi. Scale bar, 20 µm. c, d Refined RIP-seq of SARS-CoV-2 RNA harvested from Vero cells at 24 hpi (c) and 56 hpi (d) showing the distribution of m⁶A reads mapped to SARS-CoV-2 genome (red line). The gray line represents the baseline signal from input samples, and green rectangles along the x-axis show m⁶A peaks. Data are representative of n = 2 determinations. e miCLIP revealed m⁶A sites at single-base resolution across SARS-CoV-2 genome. The ratio of C-to-T transitions of input samples and immunoprecipitation samples of miCLIP, and the distribution of SARS-CoV-2 reads of immunoprecipitation samples by RIP-seq are represented by gray line, red line and pink line, respectively. The green dots show m⁶A sites that locate within the identified m⁶A peaks and are identified in both two biological replicates of miCLIP. A schematic diagram of the SARS-CoV-2 genome is shown below to indicate the location of the m⁶A-enriched sequences.