PT  - JOURNAL ARTICLE
AU  - Jarrett Smith
AU  - Deepika Calidas
AU  - Helen Schmidt
AU  - Tu Lu
AU  - Dominique Rasoloson
AU  - Geraldine Seydoux
TI  - Spatial patterning of P granules by RNA-induced phase separation of the intrinsically-disordered protein MEG-3
AID  - 10.1101/073908
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 073908
4099  - http://biorxiv.org/content/early/2016/09/07/073908.short
4100  - http://biorxiv.org/content/early/2016/09/07/073908.full
AB  - RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro. In vivo, MEG-3 forms a posterior-rich concentration gradient that is anti-correlated with a gradient in the RNA-binding protein MEX-5. MEX-5 is necessary and sufficient to suppress MEG-3 granule formation in vivo, and suppresses RNA-induced MEG-3 phase separation in vitro. Our findings support a model whereby MEX-5 functions as an mRNA sink to locally suppress MEG-3 phase separation and drive P granule asymmetry.HIGHLIGHTS- The intrinsically-disordered protein MEG-3 is essential for localized assembly of P granules in C. elegans zygotes.- MEG-3 binds RNA and RNA stimulates MEG-3 phase separation.- The RNA-binding protein MEX-5 inhibits MEG-3 granule assembly in the anterior cytoplasm by sequestering RNA.