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/mouseₐtlas).
Lei et al. (Thu,) studied this question.
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