Dynamic regulation of alternative polyadenylation by PQBP1 during neurogenesis
Xian Liu,
Hao Xie,
Wenhua Liu,
Jian Zuo,
Song Li,
Yao Tian,
Jingrong Zhao,
Meizhu Bai,
Jinsong Li,
Lan Bao,
Junhai Han,
Zi Chao Zhang
Affiliations
Xian Liu
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China
Hao Xie
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China
Wenhua Liu
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China
Jian Zuo
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China
Song Li
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China
Yao Tian
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China
Jingrong Zhao
Xu-Hui Central Hospital, Shanghai 200031, China
Meizhu Bai
State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
Jinsong Li
State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
Lan Bao
State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
Junhai Han
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China; Corresponding author
Zi Chao Zhang
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210096, China; Corresponding author
Summary: Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3′ untranslated regions (3′ UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders.
