- Title
- LncRNA GIRGL drives CAPRIN1-mediated phase separation to suppress glutaminase-1 translation under glutamine deprivation
- Creator
- Wang, Ruijie; Cao, Leixi; Thorne, Rick Francis; Zhang, Xu Dong; Li, Jinming; Shao, Fengmin; Zhang, Lirong; Wu, Mian
- Relation
- NHMRC.1147271.1147271 http://purl.org/au-research/grants/nhmrc/1147271
- Relation
- Science Advances Vol. 7, Issue 13, no. eabe5708
- Publisher Link
- http://dx.doi.org/10.1126/sciadv.abe5708
- Publisher
- American Association for the Advancement of Science (AAAS)
- Resource Type
- journal article
- Date
- 2021
- Description
- 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.
- Subject
- glutamate; glutamine; starvation; cancer cells
- Identifier
- http://hdl.handle.net/1959.13/1433555
- Identifier
- uon:39285
- Identifier
- ISSN:2375-2548
- Language
- eng
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