BCAS2 promotes primitive hematopoiesis by sequestering β-catenin within the nucleus

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/{beta}-catenin signal, which is required for hematopoietic progenitor differentiation, is significantly decreased upon depletion of bcas2 in zebrafish embryos and mouse embryonic fibroblasts (MEFs). Interestingly, BCAS2 deficiency has no obvious impact on the splicing efficiency of {beta}-catenin pre-mRNA, while significantly attenuating {beta}-catenin nuclear accumulation. Moreover, we find that BCAS2 directly binds to {beta}-catenin via its coiled-coil domains, thereby sequestering {beta}-catenin within the nucleus. Thus, our results uncover a previously unknown function of BCAS2 in promoting Wnt signaling by enhancing {beta}-catenin nuclear retention during primitive hematopoiesis.