Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS.
Abstract
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.
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Linked Datasets (1)
Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS
Homo sapiens52 data files
| File | Type | Size |
|---|---|---|
| 02_K562_LUC7L2_WT_Glu.bam | RNA-Seq | 1.1 GB |
| 02_K562_LUC7L2_WT_Glu.bam | RNA-Seq | 1.1 GB |
| 03_K562_LUC7L2_WT_Glu.bam | RNA-Seq | 1.2 GB |
| 03_K562_LUC7L2_WT_Glu.bam | RNA-Seq | 1.2 GB |
| 04_HeLa_LUC7L2_WT_Glu_B.bam | RNA-Seq | 2.5 GB |
| 04_HeLa_LUC7L2_WT_Glu_B.bam | RNA-Seq | 2.5 GB |
| 04_K562_LUC7L2_WT_GAL.bam | RNA-Seq | 1.2 GB |
| 04_K562_LUC7L2_WT_GAL.bam | RNA-Seq | 1.2 GB |
| 04_K562_LUC7L2_WT_Glu_B.bam | RNA-Seq | 1.7 GB |
| 04_K562_LUC7L2_WT_Glu_B.bam | RNA-Seq | 1.7 GB |
| 05_K562_LUC7L2_WT_GAL.bam | RNA-Seq | 958.6 MB |
| 05_K562_LUC7L2_WT_GAL.bam | RNA-Seq | 958.6 MB |
| 06_K562_LUC7L2_WT_GAL.bam | RNA-Seq | 1.2 GB |
| 06_K562_LUC7L2_WT_GAL.bam | RNA-Seq | 1.2 GB |
| 07_K562_LUC7L2_KO_Glu.bam | RNA-Seq | 1.1 GB |
| 07_K562_LUC7L2_KO_Glu.bam | RNA-Seq | 1.1 GB |
| 08_K562_LUC7L2_KO_Glu.bam | RNA-Seq | 1.3 GB |
| 08_K562_LUC7L2_KO_Glu.bam | RNA-Seq | 1.3 GB |
| 09_K562_LUC7L2_KO_Glu.bam | RNA-Seq | 1.3 GB |
| 09_K562_LUC7L2_KO_Glu.bam | RNA-Seq | 1.3 GB |
| 10_HeLa_LUC7L2_WT_Glu.bam | RNA-Seq | 1.2 GB |
| 10_HeLa_LUC7L2_WT_Glu.bam | RNA-Seq | 1.2 GB |
| 12_HeLa_LUC7L2_WT_Glu.bam | RNA-Seq | 1.2 GB |
| 12_HeLa_LUC7L2_WT_Glu.bam | RNA-Seq | 1.2 GB |
| 13_HeLa_LUC7L2_WT_GAL.bam | RNA-Seq | 1.2 GB |
| 13_HeLa_LUC7L2_WT_GAL.bam | RNA-Seq | 1.2 GB |
| 14_HeLa_LUC7L2_WT_GAL.bam | RNA-Seq | 1.1 GB |
| 14_HeLa_LUC7L2_WT_GAL.bam | RNA-Seq | 1.1 GB |
| 15_HeLa_LUC7L2_WT_GAL.bam | RNA-Seq | 1.1 GB |
| 15_HeLa_LUC7L2_WT_GAL.bam | RNA-Seq | 1.1 GB |
| 16_HeLa_LUC7L2_KO_Glu.bam | RNA-Seq | 1.1 GB |
| 16_HeLa_LUC7L2_KO_Glu.bam | RNA-Seq | 1.1 GB |
| 17_HeLa_LUC7L2_KO_Glu.bam | RNA-Seq | 1.4 GB |
| 17_HeLa_LUC7L2_KO_Glu.bam | RNA-Seq | 1.4 GB |
| 18_HeLa_LUC7L2_KO_Glu.bam | RNA-Seq | 1.2 GB |
| 18_HeLa_LUC7L2_KO_Glu.bam | RNA-Seq | 1.2 GB |
| LUC7L2_HeLa_CLIP1_S6_L008_R1_001.fastq.gz | RIP-Seq | 651.8 MB |
| LUC7L2_HeLa_CLIP1_S6_L008_R1_001.fastq.gz | RIP-Seq | 651.8 MB |
| LUC7L2_HeLa_CLIP2_S8_L008_R1_001.fastq.gz | RIP-Seq | 611.5 MB |
| LUC7L2_HeLa_CLIP2_S8_L008_R1_001.fastq.gz | RIP-Seq | 611.5 MB |
| LUC7L2_HeLa_INPUT1_S5_L008_R1_001.fastq.gz | RIP-Seq | 340.7 MB |
| LUC7L2_HeLa_INPUT1_S5_L008_R1_001.fastq.gz | RIP-Seq | 340.7 MB |
| LUC7L2_HeLa_INPUT2_S7_L008_R1_001.fastq.gz | RIP-Seq | 245.2 MB |
| LUC7L2_HeLa_INPUT2_S7_L008_R1_001.fastq.gz | RIP-Seq | 245.2 MB |
| LUC7L2_K562_CLIP1_S2_L008_R1_001.fastq.gz | RIP-Seq | 560.1 MB |
| LUC7L2_K562_CLIP1_S2_L008_R1_001.fastq.gz | RIP-Seq | 560.1 MB |
| LUC7L2_K562_CLIP2_S4_L008_R1_001.fastq.gz | RIP-Seq | 813.1 MB |
| LUC7L2_K562_CLIP2_S4_L008_R1_001.fastq.gz | RIP-Seq | 813.1 MB |
| LUC7L2_K562_INPUT1_S1_L008_R1_001.fastq.gz | RIP-Seq | 260.6 MB |
| LUC7L2_K562_INPUT1_S1_L008_R1_001.fastq.gz | RIP-Seq | 260.6 MB |
| LUC7L2_K562_INPUT2_S3_L008_R1_001.fastq.gz | RIP-Seq | 244.6 MB |
| LUC7L2_K562_INPUT2_S3_L008_R1_001.fastq.gz | RIP-Seq | 244.6 MB |
Potentially Related Datasets (2)
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.