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

文献类型: 外文期刊

作者: Wen, Qiuhan 1 ; Wang, Zhen 1 ; Bao, Qi 1 ; Ding, Tianli 1 ; Zhang, Haihan 3 ; Li, Jianbo 4 ; Liu, Zhuang 5 ; Huang, Jieping 2 ; Yi, Guoqiang 1 ;

作者机构: 1.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch, Guangdong Lab Lingnan Modern Agr,Key Lab Livestock, Shenzhen 518124, Peoples R China

2.Guangxi Univ, Coll Anim Sci & Technol, State Key Lab Conservat & Utilizat Subtrop Agrobio, Guangxi Key Lab Anim Breeding Dis Control & Preven, Nanning 530004, Peoples R China

3.Hunan Agr Univ, Coll Anim Sci & Technol, Changsha 410128, Peoples R China

4.Guangdong Acad Agr Sci, Agrobiol Gene Res Ctr, State Key Lab Swine & Poultry Breeding Ind, Guangzhou 510640, Peoples R China

5.Karolinska Inst, Ctr Mol Med, Dept Med Solna, Dermatol & Venereol Div, S-17176 Stockholm, Sweden

6.Chinese Acad Agr Sci, Kunpeng Inst Modern Agr Foshan, Agr Genom Inst Shenzhen, Foshan 528226, Peoples R China

7.Bama Yao Autonomous Cty Rural Revitalizat Res Inst, Bama 547500, Peoples R China

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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