Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
RNA. 2011 Apr;17(4):639-51. doi: 10.1261/rna.2310111. Epub 2011 Feb 22.
Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs after the second larval stage in response to environmental stimuli encountered during the first two larval stages. Dauer larvae are stress resistant and long lived, permitting survival in harsh conditions. When environmental conditions improve, dauer larvae re-enter development, and progress through two post-dauer larval stages to adulthood. Strikingly, all of these life history options (whether continuous or interrupted) involve an identical pattern and sequence of cell division and cell fates. To identify microRNAs with potential functions in buffering development in the context of C. elegans life history options, we used multiplex real-time PCR to assess the expression of 107 microRNAs throughout development in both continuous and interrupted life histories. We identified 17 microRNAs whose developmental profile of expression is affected by dauer life history and/or L1 diapause, compared to continuous development. Hence these microRNAs could function to regulate gene expression programs appropriate for different life history options in the developing worm.
动物已经进化出了确保发育结果对环境变化具有稳健性的机制。microRNA 的表达可能有助于发育稳健性,因为 microRNA 是发育基因表达的关键转录后调控因子,并且可以影响多个靶基因的表达。秀丽隐杆线虫为研究发育对环境条件的反应提供了一个极好的模型。在有利的环境中,秀丽隐杆线虫幼虫迅速而连续地通过四个幼虫阶段发育。相比之下,在不利的条件下,幼虫发育可能在两个滞育阶段之一中断:当没有食物时,胚胎孵化时发生 L1 滞育,而 dauer 滞育则发生在第一两个幼虫阶段遇到环境刺激后,在第二幼虫阶段之后。 dauer 幼虫具有抗应激和长寿的能力,允许在恶劣条件下生存。当环境条件改善时, dauer 幼虫重新进入发育,并通过两个后 dauer 幼虫阶段进入成年期。引人注目的是,所有这些生命史选项(无论是连续的还是中断的)都涉及到相同的细胞分裂和细胞命运模式和顺序。为了鉴定在秀丽隐杆线虫生命史选择的背景下具有缓冲发育功能的 microRNA,我们使用多重实时 PCR 评估了 107 个 microRNA 在连续和中断生命史中的发育过程中的表达。我们鉴定了 17 个 microRNA,其发育表达谱受到 dauer 生命史和/或 L1 滞育的影响,与连续发育相比。因此,这些 microRNA 可以调节发育中的蠕虫不同生命史选择的基因表达程序。