LncRNA GIRGL drives CAPRIN1-mediated phase separation to suppress glutaminase-1 translation under glutamine deprivation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33762340.
- Also identified by DOI 10.1126/sciadv.abe5708 and PMC identifier 7990344.
- Licence recorded as CC BY-NC.
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Abstract
Glutamine constitutes an essential source of both carbon and nitrogen for numerous biosynthetic processes. The first and rate-limiting step of glutaminolysis involves the generation of glutamate from glutamine, catalyzed by glutaminase-1 (GLS1). Shortages of glutamine result in reductions in GLS1, but the underlying mechanisms are not fully known. Here, we characterize a long noncoding RNA, GIRGL (glutamine insufficiency regulator of glutaminase lncRNA), that is induced upon glutamine starvation. Manipulating GIRGL revealed a relationship between its expression and the translational suppression of GLS1. Cellular GIRGL levels are balanced by a combination of transactivation by c-JUN together with negative stability regulation via HuR/Ago2. Increased levels of GIRGL in the absence of glutamine drive formation of a complex between dimers of CAPRIN1 and GLS1 mRNA, serving to promote liquid-liquid phase separation of CAPRIN1 and inducing stress granule formation. Suppressing GLS1 mRNA translation enables cancer cells to survive under prolonged glutamine deprivation stress.