[초청강연] Defining context-dependent proteomes of stress granules using BioID approach

Defining context-dependent proteomes of stress granules using BioID approach
Sean Millar 1,2 , Karl Schreiber 2 , Sarah Zhang 3 , Ji-Young Youn 1,2
1 Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
2 Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4,
Canada
3 Department of Physiology, University of Toronto, Toronto, ON, Canada
4 Terrence Donnelly Centre for Cellular Biomolecular Research, University of Toronto, 160
College Street, Toronto, Ontario M5S 3E1, Canada.

Living organisms face a variety of stressors that challenge the internal balance of their
cells and have developed coping mechanisms to overcome them. One important coping
mechanism involves shutting down the production of proteins and diverting the resources
into protective compartments called stress granules. Transcripts released from the
polysomes coalesce with proteins to form stress granules via multivalent interactions.
Stress granules formed under different stress conditions show variations in their make-up,
however, it is unknown to what extent they differ and how these variations influence
context-specific functions of stress granules.
To determine the proteomes of stress granules formed in different stress conditions, we
utilize BioID approach, a powerful method that can identify proteins proximal to your
protein of interest in cellular context. Using a group of bait proteins that effectively label
over 50% of the known stress granule proteome, we performed BioID labeling during
two different stress conditions, oxidative and hyperosmotic stress. Among ~450 high-
confident proximal interactors (preys) identified, we find that over 30% of preys show
significant changes, revealing a pool of dynamic associations and dissociations. The
proteins recruited to stress granules are specific to each stressor, implicating specialized
functions of stress granules, fine-tuned to the type of stress. We find that preys involved
in translation repression or mRNA decay lose proximity with stress granule proteins
regardless of the type of stress. Losing contact with these components may enable stress
granules proteins to protect transcripts during stress. Overall, our stress-BioID data reveal
shared or context-specific composition changes in stress granule proteomes.