Vasa nucleates asymmetric translation along the mitotic spindle during unequal cell divisions

Abstract

AbstractmRNA translation on the spindle is hypothesized to be an essential strategy for the localized production of cell regulators. This mechanism may be important particularly in early embryonic cells, which have a large diffusion volume and that undergo rapid cell divisions. Evidence to test such a hypothesis has been, however, limited. Here, we use an embryo with both symmetric and asymmetric cell divisions and manipulate Vasa protein, an RNA-helicase, on the spindle in live sea urchin embryos. We learned that the spindle serves as a major site of translation and that protein synthesis within a single spindle can be unequal and help drive asymmetric cell divisions during embryogenesis. Recruiting Vasa to the ectopic sub-cellular region induced a new site of translation, disturbed asymmetric translation on the spindle, and changed the cell fate. Based on these observations, we conclude that Vasa functions in localized translation, which provides a spatiotemporal control in protein synthesis and is essential for rapidly developing embryonic cells.

The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells

“…This region is evolutionarily conserved yet distinct from other DDX helicases (Fig. 4c) 9 , and was also recently reported to be critical for Vasa's function in embryonic cells of the sea urchin 22 . We, therefore, hypothesize the C3 region is critical for DDX4's activity in somatic cells.…”

“…Especially in H69AR and SHP77 cells that share a mesenchymal morphology and are partially adherent, DDX4 is stained in the cytoplasm and on the mitotic apparatus. DDX4’s localization to the mitotic apparatus was previously seen in hematopoietic cancer cell lines 25 as well as sea urchin embryonic cells 20 , 22 , suggesting DDX4’s possible conserved function among various cells and organisms.

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“…This implies that DDX4 expression facilitates tumorigenesis only in certain cell types that are equipped to tolerate its higher expression, while other cell types may not tolerate DDX4 expression and die immediately. Indeed, DDX4 expression in somatic cells is usually low and tightly regulated under normal circumstances, and its ectopic expression results in cell death, suggesting its strong potency in somatic cells 22 . This hypothesis though needs to be further tested in the future using multiple cancer cell lines that have various levels of DDX4 expressions.…”

“…Recent reports from our group as well as others, however, suggest that Vasa might also function outside of the germline, such as in embryonic development [20][21][22] , and in tissue regeneration [23][24][25] . Vasa expression in these normal somatic cells is tightly regulated and often transiently expressed during a specific step of development.…”

RNA localization to the mitotic spindle regulated by kinesin-1 and dynein is essential for early development of the sea urchin embryo

“…It was suggested that the defects in mitosis are not due to a global deficit of cyclin B protein, but rather, the localization of the cyclin B transcript and its local translation at the mitotic spindle itself is important for progression through mitosis (Groisman et al ., 2000). Since ribosomal proteins and RNAs are present at the mitotic spindle and in early cleavage stage embryos (Hassine et al ., 2020; Fernandez-Nicolas et al ., 2022), an intriguing possibility is that local translation of these transcripts encoding proteins that regulate mitosis may be essential for mitotic progression.…”