G3BP1-linked mRNA partitioning supports selective protein synthesis in response to oxidative stress

ABSTRACT: Cells limit energy-consuming mRNA translation during stress to maintain metabolic homeostasis. Sequestration of mRNAs by RNA binding proteins (RBPs) into stress granules (SGs) reduces translation, but it remains unclear whether SGs also function in partitioning of specific transcripts to polysomes (PSs) to guide selective translation and stress-adaptation in cancer. Transcripts enriched in PSs, defined by polysome fractionation and RNAseq, were compared with mRNAs complexed with the SG-nucleator protein, G3BP1, defined by spatially-restricted enzymatic tagging. Short-term oxidative stress profoundly altered mRNA translation by promoting selective enrichment of transcripts within SGs or PSs. G3BP1 participates in this compartmentalisation by sequestering transcripts in SGs. Under stress, G3BP1-bound transcripts are PS-depleted and encode proteins involved in mRNA translation, pro-apoptosis, and mitochondrial function. In contrast, specific PS-enriched transcripts disassociate from G3BP1 under stress to encode proteins involved in diverse cellular cytoprotective pathways. Therefore, G3BP1 partitioning guides selective translation to support stress adaptation and cell survival.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Syam Prakash Somasekharan  

LAB HEAD: Syam Prakash Somasekharan

PROVIDER: PXD015491 | Pride | 2020-04-30

REPOSITORIES: Pride