Multitissue single-nucleus RNA-seq reveals cell type-specific regulatory patterns of alternative polyadenylation in pigs

文献类型： 外文期刊

第一作者： Wen, Qiuhan

作者： Wen, Qiuhan;Wang, Zhen;Bao, Qi;Ding, Tianli;Yi, Guoqiang;Wen, Qiuhan;Huang, Jieping;Zhang, Haihan;Li, Jianbo;Liu, Zhuang;Yi, Guoqiang;Yi, Guoqiang

作者机构：

期刊名称：GENOME RESEARCH （ 影响因子：5.5； 五年影响因子：7.3 ）

ISSN： 1088-9051

年卷期： 2025 年 35 卷 9 期

页码：

收录情况： SCI

摘要： As an important posttranscriptional modification mechanism, alternative polyadenylation (APA) plays a crucial role in gene regulation and phenotypic diversity. Whereas extensive studies have explored the global APA landscape using bulk RNA-seq data, in-depth analyses of APA events at the single-cell level remain limited-particularly in farm animals. In this study, we construct a comprehensive APA atlas for 261 cell types across 19 porcine tissues based on single-nucleus RNA sequencing (snRNA-seq) data. This analysis reveals tissue- and cell type-specific patterns of APA. We find that many genes display a clear correlation between the average length of 3 ' untranslated regions (3 ' UTRs) and expression levels in various cell types, with most showing a negative correlation. Early cell types within the developmental lineage, such as spermatogonia and satellite cells, display longer 3 ' UTRs, especially for spermatogenesis, where 3 ' UTR lengths show significant decreasing trends along the differentiation trajectory. Notably, we find that variable 3 ' UTR lengths in the CD47 and GPD1 genes might be critical regulators during spermatogenesis and myogenesis, respectively, potentially through modulation of RNA-binding protein and miRNA binding sites. Furthermore, the SNP rs323354626, located in the 3 ' UTR of the CD47 gene, significantly impacts gene splicing and is strongly associated with reproductive phenotypes. Additionally, we observe that neuronal cells generally possess longer 3 ' UTRs-a pattern conserved across humans, mice, fruit flies, and pigs. Together, these findings enrich the single-cell atlas of pigs by adding a layer of posttranscriptional regulation to the existing gene expression data, highlighting the significant role of cell type-specific 3 ' UTR lengths in cell commitment and complex trait regulation.

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