A Human-specific Protein Regulated by Alternative Polyadenylation Shapes Uniqueness of Human Brain Development
Although new genes and regulatory events have been linked to the uniqueness of human brain development, it is unknown whether alternative polyadenylation (APA) could also be involved in 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 impacted by these events we identified ZNF271P, encoding a human-specific protein when using the distal polyadenylation site, which preferentially occurs during early brain development. The cortical organoids grown from ZNF271P-knockout human embryonic stem cells seemed to exhibit accelerated development and maturation, resulting in a significant decrease in organoid size, implicating ZNF271P in features unique to human brain development. We thus highlight APAs as new regulators in shaping the unique aspects of human brain development.
Authors
- Chunqiong Li (ORCID: https://orcid.org/0009-0007-3578-2208)
- Ni A. An (ORCID: https://orcid.org/0000-0001-9179-4106)
- Chao Yao (ORCID: https://orcid.org/0009-0002-9364-0789)
- Jianhuan Qi (ORCID: https://orcid.org/0000-0002-8056-1312)
- Chuan‐Yun Li (ORCID: https://orcid.org/0000-0002-8008-8430)
- Yuehui Lu (ORCID: https://orcid.org/0009-0002-7069-9104)
- Baoyang Hu (ORCID: https://orcid.org/0000-0003-3993-4014)
- Li Zhang (ORCID: https://orcid.org/0000-0002-0698-0754)
- Jie Zhang (ORCID: https://orcid.org/0000-0002-6269-3637)
- Fan Mo (ORCID: https://orcid.org/0000-0002-0881-0062)
- Xiangshang Li (ORCID: https://orcid.org/0000-0002-4786-3247)
- Ting Li (ORCID: https://orcid.org/0009-0001-4133-7334)
Institutions
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Southwest Forestry University (CN)
- Chinese Institute for Brain Research (CN)
- Institute of Genetics and Developmental Biology (CN)
- China Academy of Chinese Medical Sciences (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Zoology (CN)
Publication Details
- Journal
- Genomics Proteomics & Bioinformatics
- Published
- 2025-12-13
- DOI
- https://doi.org/10.1093/gpbjnl/qzaf125
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 0.00