Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

D. Allan Drummond, PhD
Assistant Professor, Biochemistry & Molecular Biology and Human Genetics
The University of Chicago

In eukaryotic cells, heat shock and other stresses trigger the accumulation of proteins and RNA into cytosolic ribonucleoprotein (RNP) stress granules marked by poly(A)-binding protein. Formation of stress granules and other RNP granules has been reported to involve multivalent RNA/protein and protein-protein interactions mediated by intrinsically disordered regions (IDRs). We have discovered that poly(A)-binding protein itself, Pab1 in yeast, autonomously forms RNP granules in vitro under physiological stress conditions. We find that, contrary to our expectations, Pab1’s highly conserved IDR modulates but is not essential for the formation of temperature-induced self-assembly in vitro and in vivo. We exploit evolutionary information to create mutant strains in which reduced Pab1 stress-induced self-assembly reduces thermotolerance. Our results illuminate a uniquely complete path from evolved sequence features, to multivalent biophysical interactions and molecular behavior, to adaptive stress-triggered RNP granule formation, and finally to organism fitness during stress.