PDF(Pubmed)
Abstract：
Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5\' leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5\' leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.
摘要：
多细胞生物由具有不同蛋白质组的特定细胞类型组成。虽然单细胞转录组分析的最新进展揭示了mRNA的差异表达，翻译谱中的细胞多样性仍未得到充分研究。通过在果蝇大脑中遗传定义的细胞中执行RNA-seq和Ribo-seq，我们在这里揭示了大量的转录后调控，在蛋白质表达水平上增加了细胞类型的区别。具体来说,我们发现蛋白质的翻译效率是神经元功能的基础，如离子通道和神经递质受体，神经胶质细胞维持在较低水平，导致它们在神经元中的优先翻译。值得注意的是,这些mRNA上核糖体足迹的分布对神经胶质中的5个领导者表现出明显的偏见。使用转基因报告菌株，我们提供的证据表明，5\'前导序列中的小上游开放阅读框赋予胶质细胞选择性翻译抑制。总的来说,这些发现强调了翻译调控在形成细胞类型区分的蛋白质组学中的深远影响,并为驱动细胞类型多样性的分子机制提供了新的见解.
