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bioRxiv · 10.1101/382838

Nematode germ granule assembly is linked to mRNA repression

Aoki, S. T.·Crittenden, S. L.·Lynch, T. R.·Bingman, C. A.·Wickens, M.·Kimble, J.
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Abstract

Cytoplasmic RNA-protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P-granules are paradigmatic liquid droplet granules and central to germ cell development. Here we analyze a key P-granule scaffolding protein, called PGL, to investigate the functional relationship between P-granule assembly and function. Using a protein-RNA tethering assay, we find that reporter mRNA expression is repressed when recruited to PGL granules. We determine the crystal structure of the PGL N-terminal region to 1.5 [A], discover its dimerization and identify key residues at the dimer interface. In vivo mutations of those interface residues prevent P-granule assembly, de-repress PGL-tethered mRNA and reduce fertility. Therefore, PGL dimerization lies at the heart of both P-granule assembly and function. Finally, we identify the P-granule-associated Argonaute WAGO-1 as crucial for repression of PGL-tethered mRNA. We conclude that P-granule function requires both assembly and localized regulators.

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Aoki, S. T., Crittenden, S. L., Lynch, T. R., Bingman, C. A., Wickens, M., Kimble, J.. 2018-08-01. Nematode germ granule assembly is linked to mRNA repression. https://doi.org/10.1101/382838

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