Calissano Mattia, Diss James K J, Latchman David S
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, United Kingdom.
FEBS Lett. 2007 May 29;581(13):2490-6. doi: 10.1016/j.febslet.2007.04.066. Epub 2007 May 2.
The post-transcriptional control of mRNA levels is a very powerful mechanism which allows cells to quickly change the amount of specific proteins. In this study, we wanted to analyze whether the Brn-3b transcription factor, essential for the proper development of mouse retinal ganglion cells, is subjected to such post-transcriptional regulation. In particular, due to its conservation amongst different species, we wanted to study the role of its 3' untranslated region (3'UTR). We show that the 3'UTR of the Brn-3b mRNA does indeed contain regulatory sequences that mediate mRNA degradation upon serum starvation-induced differentiation of ND7 neuroblastoma cells. The specific region mediating this effect has been characterized and two different microRNAs that potentially regulate the stability of Brn-3b have been identified. Moreover we show that Dicer, one of the key enzymes in the production of microRNAs, is strongly up-regulated in ND7 cells subjected to differentiation.
mRNA水平的转录后调控是一种非常强大的机制,它使细胞能够快速改变特定蛋白质的数量。在本研究中,我们想分析对小鼠视网膜神经节细胞正常发育至关重要的Brn-3b转录因子是否受到这种转录后调控。特别是,由于其在不同物种间的保守性,我们想研究其3'非翻译区(3'UTR)的作用。我们发现,Brn-3b mRNA的3'UTR确实包含调控序列,这些序列在血清饥饿诱导ND7神经母细胞瘤细胞分化时介导mRNA降解。介导这种效应的特定区域已被鉴定,并且已确定了两种可能调节Brn-3b稳定性的不同微小RNA。此外,我们还表明,微小RNA产生过程中的关键酶之一Dicer在经历分化的ND7细胞中强烈上调。