Genome Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Departamento de Fisiología, Biología Molecular y Celular, FCEyN, Universidad de Buenos Aires, Buenos Aires, Argentina.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton CB10 1SD, UK.
Curr Biol. 2018 Nov 19;28(22):3547-3561.e9. doi: 10.1016/j.cub.2018.09.026. Epub 2018 Nov 1.
Long non-coding RNAs (lncRNAs) can often function in the regulation of gene expression during development; however, their generality as essential regulators in developmental processes and organismal phenotypes remains unclear. Here, we performed a tailored investigation of lncRNA expression and function during Drosophila embryogenesis, interrogating multiple stages, tissue specificity, nuclear localization, and genetic backgrounds. Our results almost double the number of annotated lncRNAs expressed at these embryonic stages. lncRNA levels are generally positively correlated with those of their neighboring genes, with little evidence of transcriptional interference. Using fluorescent in situ hybridization, we report the spatiotemporal expression of 15 new lncRNAs, revealing very dynamic tissue-specific patterns. Despite this, deletion of selected lncRNA genes had no obvious developmental defects or effects on viability under standard and stressed conditions. However, two lncRNA deletions resulted in modest expression changes of a small number of genes, suggesting that they fine-tune expression of non-essential genes. Several lncRNAs have strain-specific expression, indicating that they are not fixed within the population. This intra-species variation across genetic backgrounds may thereby be a useful tool to distinguish rapidly evolving lncRNAs with as yet non-essential roles.
长非编码 RNA(lncRNA)在发育过程中通常可以在基因表达的调控中发挥作用;然而,它们作为发育过程和生物体表型中必要调控因子的普遍性仍不清楚。在这里,我们在果蝇胚胎发生过程中进行了 lncRNA 表达和功能的定制研究,研究了多个阶段、组织特异性、核定位和遗传背景。我们的结果使在这些胚胎阶段表达的注释 lncRNA 的数量几乎增加了一倍。lncRNA 水平通常与它们相邻基因的水平呈正相关,几乎没有转录干扰的证据。通过荧光原位杂交,我们报告了 15 个新 lncRNA 的时空表达,揭示了非常动态的组织特异性模式。尽管如此,在标准和应激条件下,删除选定的 lncRNA 基因并没有明显的发育缺陷或对存活率的影响。然而,两个 lncRNA 的缺失导致少数基因的表达水平发生微小变化,表明它们可以精细调节非必需基因的表达。一些 lncRNA 具有菌株特异性表达,表明它们在种群中不是固定的。因此,这种跨遗传背景的种内变异可能是区分具有尚未确定的非必需作用的快速进化 lncRNA 的有用工具。