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DDX1 vesicles control calcium-dependent mitochondrial activity in mouse embryos

Yixiong Wang, Lubna Yasmin, Lei Li, Pinzhang Gao, Xia Xu, Xuejun Sun and Roseline Godbout ()
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Yixiong Wang: University of Alberta
Lubna Yasmin: University of Alberta
Lei Li: University of Alberta
Pinzhang Gao: University of Alberta
Xia Xu: University of Alberta
Xuejun Sun: University of Alberta
Roseline Godbout: University of Alberta

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31497-9

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