Sahoo, B. R.; Deng, X.; Wong, E. L.; Clark, N.; Yang, H.; Subramanian, V.; Guzman, B. B.; Harris, S. E.; Dehury, B.; Miyashita, E.; Saito, H.; Dominguez, D.; Bardwell, J. C.

Small EDRK-Rich Factor (SERF) is a member of a family of partially disordered proteins whose normal biological function is unclear apart from evidence they can speed disease-related amyloid formation. We show here that human SERF2 binds specifically to non-canonical RNA structures known as G-quadruplexes and plays an important role in stress granule formation. In cells, SERF2 colocalizes with stress granule marker proteins, and its depletion significantly affects stress granule size and abundance. In vitro, SERF2 undergoes liquid-liquid phase transitions in the presence of RNA G-quadruplexes. Structural analysis of the interactions between SERF2 and RNA G4 quadruplexes gives us a high-resolution view of the multivalent interactions and protein and RNA conformational changes that appear to represent some of the early steps in liquid-liquid phase transitions and stress granule formation.