Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
PLoS One. 2009 Nov 30;4(11):e8063. doi: 10.1371/journal.pone.0008063.
Notch receptor regulates differentiation of almost all tissues and organs during animal development. Many mechanisms function at the protein level to finely regulate Notch activity. Here we provide evidence for Notch regulation at an earlier step - mRNA 3' processing. Processing at the Notch consensus polyadenylation site appears by default to be suppressed in Drosophila embryos. Interference with this suppression, by a mutation, results in increased levels of polyadenylated Notch mRNA, excess Notch signaling, and severe developmental defects. We propose that Notch mRNA 3' processing is negatively regulated to limit the production of Notch protein and render it a controlling factor in the generation of Notch signaling.
Notch 受体在动物发育过程中调节几乎所有组织和器官的分化。许多机制在蛋白质水平上发挥作用,以精细调节 Notch 的活性。在这里,我们提供 Notch 在更早阶段调节的证据 - mRNA 3' 加工。在果蝇胚胎中,Notch 保守多聚腺苷酸化位点的加工默认受到抑制。通过突变干扰这种抑制会导致多聚腺苷酸化的 Notch mRNA 水平升高、Notch 信号过度激活和严重的发育缺陷。我们提出 Notch mRNA 3' 加工受到负调控,以限制 Notch 蛋白的产生,并使其成为 Notch 信号产生的控制因素。