Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Genetics. 2022 Sep 30;222(2). doi: 10.1093/genetics/iyac099.
The regulation of stem cell survival, self-renewal, and differentiation is critical for the maintenance of tissue homeostasis. Although the involvement of signaling pathways and transcriptional control mechanisms in stem cell regulation have been extensively investigated, the role of post-transcriptional control is still poorly understood. Here, we show that the nuclear activity of the RNA-binding protein Second Mitotic Wave Missing is critical for Drosophila melanogaster intestinal stem cells and their daughter cells, enteroblasts, to maintain their progenitor cell properties and functions. Loss of swm causes intestinal stem cells and enteroblasts to stop dividing and instead detach from the basement membrane, resulting in severe progenitor cell loss. swm loss is further characterized by nuclear accumulation of poly(A)+ RNA in progenitor cells. Second Mitotic Wave Missing associates with transcripts involved in epithelial cell maintenance and adhesion, and the loss of swm, while not generally affecting the levels of these Second Mitotic Wave Missing-bound mRNAs, leads to elevated expression of proteins encoded by some of them, including the fly ortholog of Filamin. Taken together, this study indicates a nuclear role for Second Mitotic Wave Missing in adult stem cell maintenance, raising the possibility that nuclear post-transcriptional regulation of mRNAs encoding cell adhesion proteins ensures proper attachment of progenitor cells.
干细胞的存活、自我更新和分化的调控对于组织稳态的维持至关重要。尽管信号通路和转录控制机制在干细胞调控中的作用已经得到了广泛的研究，但翻译后调控的作用仍知之甚少。在这里，我们表明 RNA 结合蛋白 Second Mitotic Wave Missing 的核活性对于黑腹果蝇肠道干细胞及其子细胞 enteroblast 维持其祖细胞特性和功能至关重要。swm 的缺失导致肠道干细胞和 enteroblast 停止分裂，而从基底膜上脱落，导致祖细胞大量丢失。swm 的缺失进一步表现为多聚（A）+ RNA 在祖细胞中的核积累。Second Mitotic Wave Missing 与参与上皮细胞维持和黏附的转录本相关联，而 swm 的缺失虽然通常不会影响这些与 Second Mitotic Wave Missing 结合的 mRNAs 的水平，但会导致其中一些 mRNAs 编码的蛋白质表达水平升高，包括果蝇 Filamin 的同源物。总之，这项研究表明 Second Mitotic Wave Missing 在成体干细胞维持中的核作用，提出了核转录后调控编码细胞黏附蛋白的 mRNAs 的可能性，以确保祖细胞的正确附着。
