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Publication

Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS.

Molecular cell | 2021

Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative expression and balance of these two pathways is unknown. Here, we focus on genes whose loss leads to an increase in OXPHOS activity. Unexpectedly, this class of genes is enriched for components of the pre-mRNA splicing machinery, in particular for subunits of the U1 snRNP. Among them, we show that LUC7L2 represses OXPHOS and promotes glycolysis by multiple mechanisms, including (1) splicing of the glycolytic enzyme PFKM to suppress glycogen synthesis, (2) splicing of the cystine/glutamate antiporter SLC7A11 (xCT) to suppress glutamate oxidation, and (3) secondary repression of mitochondrial respiratory supercomplex formation. Our results connect LUC7L2 expression and, more generally, the U1 snRNP to cellular energy metabolism.

Pubmed ID: 33852893 RIS Download

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Associated grants

Agency: NIGMS NIH HHS, United States
Id: T32 GM007287
Agency: Howard Hughes Medical Institute, United States
Agency: NIGMS NIH HHS, United States
Id: R35 GM122455
Agency: NHGRI NIH HHS, United States
Id: U41 HG009889
Agency: NHGRI NIH HHS, United States
Id: R01 HG004659
Agency: NIGMS NIH HHS, United States
Id: F32 GM133047
Agency: NIGMS NIH HHS, United States
Id: R01 GM085319

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