REGULATION OF P GRANULE PHASE SEPARATION AND DYNAMICS

RNA granules;Phase Separation;Biology

Smith, Jarrett VCole, Phillip ;

Johns Hopkins University

关键词: RNA granules;    Phase Separation;    Biology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60913/SMITH-DISSERTATION-2018.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

RNA granules are assemblies of RNA and RNA-binding proteins concentrated in cells without a surrounding membrane. Many RNA granules exhibit dynamic behavior in vivo and are able to go through cycles of controlled assembly and disassembly. In the worm Caenorhabditis elegans (C. elegans), a particular type of RNA granule known as a P granule goes through a series of temporally and spatially controlled disassembly and reassembly reactions resulting in proper localization to the germline. Here we use P granules to study the mechanisms underlying these highly regulated dynamics. We provide evidence for a model in which MEX-5, an RNA binding protein, inhibits P granule assembly by binding to and sequestering available RNA from critical P granule components. We identify the intrinsically disordered domain containing protein MEG-3 as a critical component of P granules and provide evidence that the interaction between MEG-3 and RNA drives P granule assembly in the cell and that this interaction is antagonized by MEX-5. We go on to show that the dynamic nature of these granules is, at least in part, due to active, energy-dependent disassembly. This work provides several key insights into the regulation of P granule dynamics that may prove to be generalizable for many types of RNA granules.