Tadros Wael, Goldman Aaron L, Babak Tomas, Menzies Fiona, Vardy Leah, Orr-Weaver Terry, Hughes Timothy R, Westwood J Timothy, Smibert Craig A, Lipshitz Howard D
Graduate Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Dev Cell. 2007 Jan;12(1):143-55. doi: 10.1016/j.devcel.2006.10.005.
In animals, egg activation triggers a cascade of posttranscriptional events that act on maternally synthesized RNAs. We show that, in Drosophila, the PAN GU (PNG) kinase sits near the top of this cascade, triggering translation of SMAUG (SMG), a multifunctional posttranscriptional regulator conserved from yeast to humans. Although PNG is required for cytoplasmic polyadenylation of smg mRNA, it regulates translation via mechanisms that are independent of its effects on the poly(A) tail. Analyses of mutants suggest that PNG relieves translational repression by PUMILIO (PUM) and one or more additional factors, which act in parallel through the smg mRNA's 3' untranslated region (UTR). Microarray-based gene expression profiling shows that SMG is a major regulator of maternal transcript destabilization. SMG-dependent mRNAs are enriched for gene ontology annotations for function in the cell cycle, suggesting a possible causal relationship between failure to eliminate these transcripts and the cell cycle defects in smg mutants.
在动物中，卵子激活会触发一系列作用于母源合成RNA的转录后事件。我们发现，在果蝇中，盘古（PNG）激酶处于这一信号级联反应的顶端附近，触发多功能转录后调节因子斯马乌格（SMG）的翻译，SMG从酵母到人类都是保守的。虽然PNG是smg mRNA细胞质多聚腺苷酸化所必需的，但它通过独立于其对多聚腺苷酸尾影响的机制来调节翻译。对突变体的分析表明，PNG通过抑制 pumilio（PUM）和一个或多个其他因子来解除翻译抑制，这些因子通过smg mRNA的3'非翻译区（UTR）并行发挥作用。基于微阵列的基因表达谱分析表明，SMG是母源转录本去稳定化的主要调节因子。依赖SMG的mRNA在细胞周期功能的基因本体注释中富集，这表明未能消除这些转录本与smg突变体中的细胞周期缺陷之间可能存在因果关系。
