A Human-specific Protein Regulated by Alternative Polyadenylation Shapes Uniqueness of Human Brain Development
Year: 2025
Type: article
Abstract: Although new genes and regulatory events have been linked to the uniqueness of human brain development, it is unknown whether alternative polyadenylation (APA) also contributes to shaping this key feature that differentiates humans from other species. Here, we present an atlas of APAs of the human brain and identified 161 development-related, open-reading-frame-disrupting APAs associated with the dynamic translation of protein products. Among the genes affected by these events, we identified ZNF271P, which encodes a human-specific protein when using the distal polyadenylation site, a site that preferentially occurs during early brain development. The cortical organoids derived from ZNF271P-knockout human embryonic stem cells seemed to exhibit accelerated development and maturation, resulting in a significant decrease in organoid size, implicating that ZNF271P is involved in features unique to human brain development. We thus highlight APAs as new regulators in shaping the unique aspects of human brain development.
Authors: Ting Li, Fan Mo, Jianhuan Qi, Chunqiong Li, Chunqiong Li, Xiangshang Li, Jie Zhang, Yingfei Lu, Chao Yao, Li Zhang, Baoyang Hu, Chuan-Yun Li, Chuan-Yun Li, Ni A An
Institutions: Chinese Academy of Sciences, Peking University, Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, State Key Laboratory of Protein and Plant Gene Research, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Chinese Institute for Brain Research
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,850
Awards: G5811777610, G8198843592
OpenAlex ID: W4417303196