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

Alexis A Jourdain, Bridget E Begg, Eran Mick, Hardik Shah, Sarah E Calvo, Owen S Skinner, Rohit Sharma, Steven M Blue, Gene W Yeo, Christopher B Burge, Vamsi K Mootha

Molecular cell · 2021 · Vol. 81 (9) · pp. 1905-1919.e12

PubMed ↗ DOI ↗ PMC full text ↗

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.

Linked datasets 1

GSE157917 GSE · via ncbi_elink
GEO ↗

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

Homo sapiens

52 data files
FileTypeSize
02_K562_LUC7L2_WT_Glu.bam RNA-Seq 1.1 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_K562_LUC7L2_WT_GAL.bam RNA-Seq 1.2 GB
04_K562_LUC7L2_WT_Glu_B.bam RNA-Seq 1.7 GB
05_K562_LUC7L2_WT_GAL.bam RNA-Seq 958.6 MB
06_K562_LUC7L2_WT_GAL.bam RNA-Seq 1.2 GB
07_K562_LUC7L2_KO_Glu.bam RNA-Seq 1.1 GB
08_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
12_HeLa_LUC7L2_WT_Glu.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
15_HeLa_LUC7L2_WT_GAL.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
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_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_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_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_INPUT2_S3_L008_R1_001.fastq.gz RIP-Seq 244.6 MB
SRR12638141_GSM4780786 RNA-Seq 1.2 GB
SRR12638142_GSM4780787 RNA-Seq 1.2 GB
SRR12638143_GSM4780788 RNA-Seq 2.5 GB
SRR12638144_GSM4780789 RNA-Seq 1.2 GB
SRR12638145_GSM4780790 RNA-Seq 1.1 GB
SRR12638146_GSM4780791 RNA-Seq 1.1 GB
SRR12638147_GSM4780792 RNA-Seq 1.1 GB
SRR12638148_GSM4780793 RNA-Seq 1.4 GB
SRR12638149_GSM4780794 RNA-Seq 1.2 GB
SRR12638150_GSM4780795 RNA-Seq 1.1 GB
SRR12638151_GSM4780796 RNA-Seq 1.2 GB
SRR12638152_GSM4780797 RNA-Seq 1.7 GB
SRR12638153_GSM4780798 RNA-Seq 1.2 GB
SRR12638154_GSM4780799 RNA-Seq 958.0 MB
SRR12638155_GSM4780800 RNA-Seq 1.2 GB
SRR12638156_GSM4780801 RNA-Seq 1.1 GB
SRR12638157_GSM4780802 RNA-Seq 1.3 GB
SRR12638158_GSM4780803 RNA-Seq 1.3 GB
SRR12819255_GSM4830581 RIP-Seq 340.0 MB
SRR12819256_GSM4830582 RIP-Seq 245.0 MB
SRR12819257_GSM4830583 RIP-Seq 260.0 MB
SRR12819258_GSM4830584 RIP-Seq 244.0 MB
SRR12819259_GSM4830585 RIP-Seq 651.0 MB
SRR12819260_GSM4830586 RIP-Seq 611.0 MB
SRR12819261_GSM4830587 RIP-Seq 560.0 MB
SRR12819262_GSM4830588 RIP-Seq 813.0 MB

Potentially related datasets 3

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.

Accession Source Title
GSM854403 GSM · GEO No title in the index
PXD021917 PXD · PRIDE No title in the index
GSE157917 GSE · GEO GEO ↗ Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS

Analysis pipelines 1

Pipeline Assay Steps Dataset
GSE157917 eCLIP Data Processing geo_data_processing eCLIP 3 GSE157917
Funding 7 grants
Grant Funder
R01 HG004659 NHGRI NIH HHS (United States)
U41 HG009889 NHGRI NIH HHS (United States)
Howard Hughes Medical Institute (United States)
T32 GM007287 NIGMS NIH HHS (United States)
R35 GM122455 NIGMS NIH HHS (United States)
F32 GM133047 NIGMS NIH HHS (United States)
R01 GM085319 NIGMS NIH HHS (United States)