<p>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 (<a href="https://zhailab.bio.sustech.edu.cn/mouse_atlas">https://zhailab.bio.sustech.edu.cn/mouse_atlas</a>).</p>

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

  • Huajie Lei,
  • Yanping Long,
  • Shasha Wu,
  • Xin Wang,
  • Yuanzheng Peng,
  • Zhijian Liu,
  • Wenqin Lu,
  • Yi Shu,
  • Hongyan Zhu,
  • Mengyun Zou,
  • Yujie Gao,
  • Yiji Xia,
  • Sisi Li,
  • Lili Ren,
  • Yingxin Fu,
  • Zheng Zhang,
  • Yan Li,
  • Jixian Zhai

摘要

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).