Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, T6G 1Z2, Canada.
Nat Commun. 2022 Jul 1;13(1):3794. doi: 10.1038/s41467-022-31497-9.
The DEAD box protein DDX1, previously associated with 3'-end RNA processing and DNA repair, forms large aggregates in the cytoplasm of early mouse embryos. Ddx1 knockout causes stalling of embryos at the 2-4 cell stages. Here, we identify a DDX1-containing membrane-bound calcium-containing organelle with a nucleic acid core. We show that aggregates of these organelles form ring-like structures in early-stage embryos which we have named Membrane Associated RNA-containing Vesicles. We present evidence that DDX1 is required for the formation of Membrane Associated RNA-containing Vesicles which in turn regulate the spatial distribution of calcium in embryos. We find that Ddx1 knockout in early embryos disrupts calcium distribution, and increases mitochondria membrane potential, mitochondrial activity, and reactive oxygen species. Sequencing analysis of embryos from Ddx1 heterozygote crosses reveals downregulation of a subset of RNAs involved in developmental and mitochondrial processes in the embryos with low Ddx1 RNA. We propose a role for Membrane Associated RNA-containing Vesicles in calcium-controlled mitochondrial functions that are essential for embryonic development.
DEAD 框蛋白 DDX1 先前与 3'-末端 RNA 加工和 DNA 修复有关，在早期小鼠胚胎的细胞质中形成大的聚集体。Ddx1 敲除导致胚胎在 2-4 细胞阶段停滞。在这里，我们鉴定了一种含有膜结合钙的细胞器，其核心含有核酸。我们表明，这些细胞器的聚集体在早期胚胎中形成环状结构，我们将其命名为膜相关 RNA 包含的囊泡。我们提供的证据表明，DDX1 是形成膜相关 RNA 包含的囊泡所必需的，而这些囊泡反过来又调节胚胎中钙的空间分布。我们发现，早期胚胎中的 Ddx1 敲除破坏了钙的分布，并增加了线粒体膜电位、线粒体活性和活性氧。来自 Ddx1 杂合子杂交胚胎的测序分析显示，在 Ddx1 RNA 水平较低的胚胎中，参与发育和线粒体过程的一组 RNA 下调。我们提出了膜相关 RNA 包含的囊泡在钙控制的线粒体功能中的作用，这些功能对于胚胎发育至关重要。
