Pan-organ poly(A) atlas reveals a post-transcriptional regulatory layer independent of RNA abundance.

Post-transcriptional regulation via the mRNA poly(A) tail is fundamental to gene expression, yet a comprehensive dataset across an entire organism is still lacking. Here, we generated a pan-organ atlas of poly(A) tail lengths across 18 murine organs using full-length nanopore sequencing that totaled 422 million reads. This dataset enables robust, single-molecule poly(A) profiling for an average of 7421 genes per sample (≥20 reads). We observed notably heterogeneous and organ-specific poly(A) tail length landscapes, ranging from profiles peaking at ~45 nt in pancreas to ~180 nt in reproductive tissues. Clustering isoforms by cross-organ poly(A) dynamics reveals functionally coherent regulatory modules that are statistically orthogonal to those derived from transcript abundance. This orthogonality is biologically informative, as poly(A) length co-regulation predicts known functional interactions even among genes with divergent expression. Together, these findings establish poly(A) tail dynamics as an independent, functionally coherent regulatory layer and provide a foundational resource for deciphering this dimension of transcriptome regulation ( https://zhailab.bio.sustech.edu.cn/mouse_atlas ).