Dataset Information

Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action.

ABSTRACT: The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a transcriptional coactivator that controls expression of metabolic/energetic genes, programming cellular responses to nutrient and environmental adaptations such as fasting, cold, or exercise. Unlike other coactivators, PGC-1α contains protein domains involved in RNA regulation such as serine/arginine (SR) and RNA recognition motifs (RRMs). However, the RNA targets of PGC-1α and how they pertain to metabolism are unknown. To address this, we performed enhanced ultraviolet (UV) cross-linking and immunoprecipitation followed by sequencing (eCLIP-seq) in primary hepatocytes induced with glucagon. A large fraction of RNAs bound to PGC-1α were intronic sequences of genes involved in transcriptional, signaling, or metabolic function linked to glucagon and fasting responses, but were not the canonical direct transcriptional PGC-1α targets such as OXPHOS or gluconeogenic genes. Among the top-scoring RNA sequences bound to PGC-1α were Foxo1, Camk1δ, Per1, Klf15, Pln4, Cluh, Trpc5, Gfra1, and Slc25a25 PGC-1α depletion decreased a fraction of these glucagon-induced messenger RNA (mRNA) transcript levels. Importantly, knockdown of several of these genes affected glucagon-dependent glucose production, a PGC-1α-regulated metabolic pathway. These studies show that PGC-1α binds to intronic RNA sequences, some of them controlling transcript levels associated with glucagon action.

SUBMITTER: Tavares CDJ

PROVIDER: S-EPMC7486754 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action.

Tavares Clint D J CDJ Aigner Stefan S Sharabi Kfir K Sathe Shashank S Mutlu Beste B Yeo Gene W GW Puigserver Pere P

Proceedings of the National Academy of Sciences of the United States of America 20200826 36

The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a transcriptional coactivator that controls expression of metabolic/energetic genes, programming cellular responses to nutrient and environmental adaptations such as fasting, cold, or exercise. Unlike other coactivators, PGC-1α contains protein domains involved in RNA regulation such as serine/arginine (SR) and RNA recognition motifs (RRMs). However, the RNA targets of PGC-1α and how they pertain to metabolism a ...[more]

PMID: 32848060

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Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action.

Publications

Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action.

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