Regulation of Alternative Polyadenylation Events by PABPC1 Affects Erythroid Progenitor Cell Expansion

Yanan Li; Yanbo Yang; Bin Hu; Zi Wang; Wei Wang; Xiaofeng He; Xusheng Wu; Sheng Lin; Narla Mohandas; Hong Liu; Jing Gong; Long Liang; Jing Liu

doi:10.1093/gpbjnl/qzaf116

Regulation of Alternative Polyadenylation Events by PABPC1 Affects Erythroid Progenitor Cell Expansion

Genomics Proteomics Bioinformatics. 2025 Nov 25:qzaf116. doi: 10.1093/gpbjnl/qzaf116. Online ahead of print.

Authors

Yanan Li^{1

2}, Yanbo Yang³, Bin Hu¹, Zi Wang¹, Wei Wang², Xiaofeng He⁴, Xusheng Wu⁴, Sheng Lin⁴, Narla Mohandas⁵, Hong Liu⁶, Jing Gong^{3

7}, Long Liang¹, Jing Liu¹

Affiliations

¹ Department of Hematology, the Second Xiangya Hospital; Molecular Biology Research Center, Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha 410013, China.
² Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
³ Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.
⁴ Shenzhen Health Development Research and Data Management Center, Shenzhen 518000, China.
⁵ Research Laboratory of Red Cell Physiology, New York Blood Center, New York, NY 10065, USA.
⁶ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Clinical Research Center for Cancer Immunotherapy, Furong Laboratory, Central South University, Changsha 410028, China.
⁷ College of Biomedicine and Health, Huazhong Agricultural University, Wuhan 430072, China.

PMID: 41289092
DOI: 10.1093/gpbjnl/qzaf116

Abstract

Erythropoiesis is precisely regulated by multilayered networks. It is crucial for maintaining steady-state hemoglobin levels and ensuring effective oxygen transport. Alternative polyadenylation (APA) is a post-transcriptional regulatory mechanism generating multiple mRNA isoforms from a single gene based on specific 3'-untranslated region sequences. While APA plays a vital role in various cellular processes, the underlying mechanism in erythropoiesis remains largely unexplored. In this study, we employed an integrative approach, combining bioinformatics analyses and experimental validations, to systematically investigate the role of APA in erythropoiesis. We mapped the APA landscape during erythroid differentiation and identified significant APA shifts essential for the differentiation of erythroid cells from burst-forming unit erythroid (BFU-E) to colony-forming unit erythroid (CFU-E). Notably, our findings highlighted polyadenylate-binding protein cytoplasmic 1 (PABPC1) as the primary regulator of APA during these stages. Functional analyses have revealed that knockdown of PABPC1 disrupts erythroid progenitor cell proliferation and differentiation. These results implicate an essential role of PABPC1 in modulating cell fate through APA regulation. Furthermore, we found that decreased PABPC1 levels increased the usage of the proximal polyadenylation sites in the TSC22D1 gene. This shift led to elevated expression of TSC22D1, uncovering a novel mechanism by which APA influences erythroid progenitor expansion and differentiation. Our findings provide novel insights into APA regulation in early erythropoiesis and suggest potential therapeutic strategies for diseases associated with erythropoietic disorders.

Keywords: Alternative polyadenylation; Erythroid progenitor; Erythropoiesis; PABPC1; TSC22D1.

© The Author(s) 2025. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.