ArticleMolecular cell2023
PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis.Nature aging · 2025Article
- Plant food-derived antioxidant nutrients in neuroprotection against chemotherapy-induced neurotoxicity: from molecular mechanisms to clinical applications.Frontiers in nutrition · 2025Review
- Nuclear mRNA decay: regulatory networks that control gene expression.Nature reviews. Genetics · 2024Review
- Co-transcriptional gene regulation in eukaryotes and prokaryotes.Nature reviews. Molecular cell biology · 2024Review
- Mitochondria in Mesenchymal Stem Cells: Key to Fate Determination and Therapeutic Potential.Stem cell reviews and reports · 2024Review
- Cardiac maturation.Journal of molecular and cellular cardiology · 2024Review
- The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.Nature communications · 2023Article
- Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
PGC-1α is well established as a metazoan transcriptional coactivator of cellular adaptation in response to stress. However, the mechanisms by which PGC-1α activates gene transcription are incompletely understood. Here, we report that PGC-1α serves as a scaffold protein that physically and functionally connects the DNA-binding protein estrogen-related receptor α (ERRα), cap-binding protein 80 (CBP80), and Mediator to overcome promoter-proximal pausing of RNAPII and transcriptionally activate stress-response genes. We show that PGC-1α promotes pausing release in a two-arm mechanism (1) by recruiting the positive transcription elongation factor b (P-TEFb) and (2) by outcompeting the premature transcription termination complex Integrator. Using mice homozygous for five amino acid changes in the CBP80-binding motif (CBM) of PGC-1α that destroy CBM function, we show that efficient differentiation of primary myoblasts to myofibers and timely skeletal muscle regeneration after injury require PGC-1α binding to CBP80. Our findings reveal how PGC-1α activates stress-response gene transcription in a previously unanticipated pre-mRNA quality-control pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.