Negative Regulation of a Ribonucleoprotein Condensate Driven by Dilute Phase Oligomerization
- klotsagroup
- Jun 20, 2023
- 2 min read
Our paper on the Negative regulation of a ribonucleoprotein condensate driven by dilute phase oligomerization just appeared on the bioaRxiv, check it out here.
Negative regulation of a ribonucleoprotein condensate driven by dilute phase oligomerization Ian Seima, Ammon E. Posey, Wilton T. Snead , Benjamin M. Stormo , Daphne Klotsa, Rohit V. Pappu, and Amy S. Gladfelter
Ribonucleoprotein bodies are exemplars of membraneless biomolecular condensates that can form via spontaneous or driven phase transitions.
The fungal protein Whi3 forms compositionally distinct ribonucleoprotein condensates that are implicated in key processes such as cell-cycle control and cell polarity. Whi3 has a modular architecture that includes a Q-rich intrinsically disordered region and a tandem RNA recognition module. Here, we uncover localized order-todisorder transitions within a 21-residue stretch of the Q-rich region. This region, which can form alpha-helical conformations, is shown to modulate protein density within Whi3-RNA condensates by driving dilute phase oligomerization. Specifically, enhancing helicity within this region enhances oligomerization in the dilute phase. This weakens the associations among disordered Qrich regions thereby diluting the concentration of Whi3 in condensates.
The opposite behavior is observed when helicity within the 21-residue stretch of the Q-rich region is abrogated. Thus, dilute phase oligomers, driven by a specific sequence motif, lead to negative regulation of the stoichiometry of protein versus RNA in the dense phase. Our findings stand in contrast to other systems where oligomerization is known to enhance the drive for phase separation. Our results highlight distinctive regulatory effects over phase behavior due to local order-to-disorder transitions within intrinsically disordered regions. This provides a way to leverage molecular scale conformational preferences and coupled intermolecular associations to regulate mesoscale phase behavior and material properties of condensates.
April 20, 2021