Maity A, McKenna W G, Muschel R J
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Cell Growth Differ. 1997 Mar;8(3):311-8.
Progression through the cell cycle in somatic eukaryotic cells is regulated by variations in the levels of cyclin proteins. These protein levels are in turn regulated by cyclical oscillations in their mRNA levels. We show here that regulation of RNA stability plays a role in the mechanisms underlying cell cycle progression. Both cyclin A and B1 messages are expressed at high levels in G2-M and at low levels in early G1. The half-lives of their messages mirror this pattern, long in G2-M (>8 h) and short in early G1 (1-2 h). However, there is evidence of specificity to these changes, because the cyclin A message becomes stable at the G1-S boundary, whereas the cyclin B1 message is unstable until later in S phase. Furthermore, although cyclin B1 mRNA levels are lowered after irradiation because of enhanced instability, cyclin A mRNA levels and message stability are unaffected by irradiation. Additional evidence of specificity was found in an analysis of cyclin E mRNA stability, which remains constant through the cell cycle, although the cyclin E message displays cell cycle-dependent changes in expression. These studies suggest that specific alterations in RNA stability are an important component in regulating the expression of cyclins A and B1 and hence in controlling the cell cycle.
体细胞真核细胞中细胞周期的进程受细胞周期蛋白水平变化的调控。而这些蛋白质水平又受其mRNA水平周期性振荡的调节。我们在此表明,RNA稳定性的调节在细胞周期进程的潜在机制中发挥作用。细胞周期蛋白A和B1的信使RNA在G2-M期高表达,在G1早期低表达。它们信使RNA的半衰期反映了这种模式,在G2-M期较长(>8小时),在G1早期较短(1-2小时)。然而,有证据表明这些变化具有特异性,因为细胞周期蛋白A的信使RNA在G1-S边界变得稳定,而细胞周期蛋白B1的信使RNA直到S期后期才稳定。此外,虽然照射后由于不稳定性增强,细胞周期蛋白B1的mRNA水平降低,但细胞周期蛋白A的mRNA水平和信使RNA稳定性不受照射影响。在对细胞周期蛋白E的mRNA稳定性分析中发现了特异性的额外证据,尽管细胞周期蛋白E的信使RNA表达呈现细胞周期依赖性变化,但其在整个细胞周期中保持恒定。这些研究表明,RNA稳定性的特定改变是调节细胞周期蛋白A和B1表达从而控制细胞周期的重要组成部分。