St-Patrick Research Group in Basic Oncology, Centre Hospitalier Universitaire de Québec-Université Laval Research Centre (L'Hôtel-Dieu de Québec), Quebec City, QC G1R 3S3, Canada; Laval University Cancer Research Centre, Quebec City, QC G1R 3S3, Canada.
St-Patrick Research Group in Basic Oncology, Centre Hospitalier Universitaire de Québec-Université Laval Research Centre (L'Hôtel-Dieu de Québec), Quebec City, QC G1R 3S3, Canada; Laval University Cancer Research Centre, Quebec City, QC G1R 3S3, Canada.
Dev Cell. 2018 Oct 22;47(2):239-247.e4. doi: 10.1016/j.devcel.2018.08.022. Epub 2018 Sep 20.
Animal germ cells possess a specific post-transcriptional regulatory context allowing the storage of maternal transcripts in the oocyte until their translation at a specific point in early development. As key regulators of gene expression, miRNAs repress translation mainly through mRNA destabilization. Thus, germline miRNAs likely use distinct ways to regulate their targets. Here, we use C. elegans to compare miRNA function within germline and somatic tissues. We show that the same miRNA displays tissue-specific gene regulatory mechanisms. While translational repression occurs in both tissues, targeted mRNAs are instead stabilized in the germline. Comparative analyses of miRNA silencing complexes (miRISC) demonstrate that their composition differs from germline to soma. We show that germline miRNA targets preferentially localize to perinuclear regions adjacent to P granules, and their repression is dependent on the core P granule component GLH-1. Together, our findings reveal the existence of different miRISC in animals that affect targeted mRNAs distinctively.
动物生殖细胞具有特定的转录后调控环境,允许母本转录本在卵母细胞中储存,直到在早期发育的特定点进行翻译。miRNAs 作为基因表达的关键调节剂,主要通过 mRNA 不稳定化来抑制翻译。因此,生殖系 miRNAs 可能使用不同的方式来调节其靶标。在这里,我们使用 C. elegans 来比较生殖系和体细胞组织中的 miRNA 功能。我们表明,相同的 miRNA 显示出组织特异性的基因调控机制。虽然在两种组织中都发生了翻译抑制,但靶向 mRNA 反而在生殖系中稳定化。对 miRNA 沉默复合物 (miRISCs) 的比较分析表明,它们的组成从生殖系到体躯有所不同。我们表明,生殖系 miRNA 靶标优先定位于靠近 P 颗粒的核周区域,并且它们的抑制依赖于核心 P 颗粒成分 GLH-1。总之,我们的研究结果揭示了在动物中存在不同的 miRISC,它们对靶标 mRNA 的影响是不同的。