Prolonged Sample Storage Reshapes the m6A Methylation Landscape Through RNA Degradation

N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA, essential for post-transcriptional regulation. MeRIP-seq is widely used for m6A profiling, but RNA degradation challenges accurate analysis. While the effects of sample handling on RNA are known, the impact of tissue sample storage durations on m6A remains unclear. We investigated how sample storage durations (0, 2, 12, 24, and 48 h at room temperature) affect RNA integrity, m6A peaks, and transcriptomes in mouse liver. RNA integrity declined with time, reducing m6A peak number and reproducibility. Prolonged storage diverged m6A profiles, increased unreported peaks, shifted RRACH motifs, and redistributed peaks to intergenic/intronic regions. Integrated data showed opposing changes in m6A and expression for some genes, suggesting storage degradation confounds epitranscriptomic interpretation. Sample storage durations are critical for m6A accuracy, emphasizing the need for standardized handling in MeRIP-seq studies.