PDF(Pubmed)
Abstract：
Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent mRNA stability in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for mRNA stability and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA stability and protein expression.
摘要：
密码子最优性的调节是细胞和组织特异性蛋白表达控制的一个日益受到重视的层面。这里,我们使用密码子修饰的报告基因显示果蝇神经干细胞分化为神经元能够从稀有密码子富集的基因中表达蛋白质.从候选人屏幕上看，我们确定了细胞质聚腺苷酸化元件结合(CPEB)蛋白Orb2是神经元中稀有密码子依赖性mRNA稳定性的正调节因子.使用RNA测序，我们发现，具有丰富Orb2结合位点的大脑中Orb2上调的mRNA具有罕见密码子偏好。从这些Orb2调控的mRNA中，我们证明稀有密码子富集对于代谢型谷氨酸受体（mGluR）的mRNA稳定性和社会行为功能很重要。我们的发现揭示了神经干细胞分化改变遗传密码调控以实现关键mRNA稳定性和蛋白质表达的分子机制。
