BCAS2 promotes primitive hematopoiesis by sequestering β-catenin within the nucleus
Year: 2024
Type: preprint
Abstract: Breast carcinoma amplified sequence 2 (BCAS2), a core component of the hPrP19 complex, plays crucial roles in various physiological and pathological processes. However, whether BCAS2 has functions other than being a key RNA-splicing regulator within the nucleus remains unknown. Here, we show that BCAS2 is essential for primitive hematopoiesis in zebrafish and mouse embryos. The activation of Wnt/β-catenin signaling, which is required for hematopoietic progenitor differentiation, is significantly decreased upon depletion of bcas2 in zebrafish embryos and mouse embryonic fibroblasts. Interestingly, BCAS2 deficiency has no obvious impact on the splicing efficiency of β-catenin pre-mRNA, while significantly attenuating β-catenin nuclear accumulation. Moreover, we find that BCAS2 directly binds to β-catenin via its coiled-coil domains, thereby sequestering β-catenin within the nucleus. Thus, our results uncover a previously unknown function of BCAS2 in promoting Wnt signaling by enhancing β-catenin nuclear retention during primitive hematopoiesis.
Source: eLife
DOI: 10.7554/elife.100497
Authors: Guozhu Ning, Yu Lin, Haixia Ma, Jiaqi Zhang, Liping Yang, Zhengyu Liu, Lei Li, Xinyu He, Qiang Wang
Institutions: Guangdong Medical College, South China University of Technology, Qiqihar Medical University, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Beijing Institute for Stem Cell and Regenerative Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4402359216