Division of Biological Sciences, University of Montana, Missoula, United States.
Elife. 2020 Aug 17;9:e52788. doi: 10.7554/eLife.52788.
Stem cells support tissue maintenance, but the mechanisms that coordinate the rate of stem cell self-renewal with differentiation at a population level remain uncharacterized. We find that two PUF family RNA-binding proteins FBF-1 and FBF-2 have opposite effects on germline stem cell dynamics: FBF-1 restricts the rate of meiotic entry, while FBF-2 promotes both cell division and meiotic entry rates. Antagonistic effects of FBFs are mediated by their distinct activities toward the shared set of target mRNAs, where FBF-1-mediated post-transcriptional control requires the activity of CCR4-NOT deadenylase, while FBF-2 is deadenylase-independent and might protect the targets from deadenylation. These regulatory differences depend on protein sequences outside of the conserved PUF family RNA-binding domain. We propose that the opposing FBF-1 and FBF-2 activities serve to modulate stem cell division rate simultaneously with the rate of meiotic entry.
干细胞支持组织维持，但协调干细胞自我更新率与群体水平分化率的机制仍未被描述。我们发现，两个 PUF 家族 RNA 结合蛋白 FBF-1 和 FBF-2 对生殖干细胞动力学有相反的影响：FBF-1 限制减数分裂进入的速度，而 FBF-2 则促进细胞分裂和减数分裂进入的速度。FBFs 的拮抗作用是通过它们对共享靶 mRNA 组的不同活性介导的，其中 FBF-1 介导的转录后控制需要 CCR4-NOT 脱腺苷酶的活性，而 FBF-2 则与脱腺苷酶无关，并且可能防止靶标脱腺苷酸化。这些调节差异取决于保守 PUF 家族 RNA 结合域之外的蛋白质序列。我们提出，相反的 FBF-1 和 FBF-2 活性同时调节干细胞分裂率和减数分裂进入率。
