TY - JOUR T1 - The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA JF - bioRxiv DO - 10.1101/2020.06.17.158121 SP - 2020.06.17.158121 AU - Jasmine Cubuk AU - Jhullian J. Alston AU - J. Jeremías Incicco AU - Sukrit Singh AU - Melissa D. Stuchell-Brereton AU - Michael D. Ward AU - Maxwell I. Zimmerman AU - Neha Vithani AU - Daniel Griffith AU - Jason A. Wagoner AU - Gregory R. Bowman AU - Kathleen B. Hall AU - Andrea Soranno AU - Alex S. Holehouse Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/12/21/2020.06.17.158121.abstract N2 - The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA binding protein critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood. Here we combine single-molecule spectroscopy with all-atom simulations to uncover the molecular details that contribute to N protein function. N protein contains three dynamic disordered regions that house putative transiently-helical binding motifs. The two folded domains interact minimally such that full-length N protein is a flexible and multivalent RNA binding protein. N protein also undergoes liquid-liquid phase separation when mixed with RNA, and polymer theory predicts that the same multivalent interactions that drive phase separation also engender RNA compaction. We offer a simple symmetry-breaking model that provides a plausible route through which single-genome condensation preferentially occurs over phase separation, suggesting that phase separation offers a convenient macroscopic readout of a key nanoscopic interaction.Competing Interest StatementThe authors have declared no competing interest. ER -