A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci

Doi, A.; Suarez, G. D.; Droste, R.; Horvitz, H. R.

doi:10.1101/2022.03.28.486141

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bioRxiv · 10.1101/2022.03.28.486141

A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci

Doi, A.·Suarez, G. D.·Droste, R.·Horvitz, H. R.

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Abstract

How cells regulate gene expression in a precise spatiotemporal manner during organismal development is a fundamental question in biology. Recent studies have demonstrated the role of transcriptional condensates in gene regulation1-5. However, little is known about the function and regulation of these transcriptional condensates in the context of animal development and physiology. We found that the evolutionarily conserved DEAD-box helicase DDX-23 controls stem cell fate in C. elegans at least in part by binding to and facilitating the condensation of MAB-10, the C. elegans homolog of mammalian NAB protein. MAB-10 is a transcriptional cofactor that functions with the EGR protein LIN-29 to regulate the transcription of genes required for exiting the cell cycle, terminal differentiation, and the larval-to-adult transition6. We suggest that DEAD-box helicase proteins function more generally during animal development to control the condensation of NAB proteins important in cell-fate decisions and that this mechanism is evolutionarily conserved. In mammals, a comparable mechanism might underlie terminal cell differentiation and when misregulated might promote cancerous growth.

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Doi, A., Suarez, G. D., Droste, R., Horvitz, H. R.. 2022-03-29. A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci. https://doi.org/10.1101/2022.03.28.486141

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