Journal
FRONTIERS IN ONCOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2018.00408
Keywords
splicing regulation; histone modifications; piruvate kinase; 2-oxoglutarate-dependent dioxidases (2-OGDD); lysine demethylases (KDM); m6A demethylase; DNA demethylases (TETs)
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Funding
- Associazione Italiana per la Ricerca sul Cancro AIRC [15273]
- Flagship project InterOmics (CNR-MIUR)
- Progetto d'Interesse Invecchiamento (CNR-MIUR)
- AMANDA project Accordo Quadro Regione Lombardia-CNR
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Alternative splicing is a pervasive mechanism that molds the transcriptome to meet cell and organism needs. However, how this layer of gene expression regulation is coordinated with other aspects of the cell metabolism is still largely undefined. Glucose is the main energy and carbon source of the cell. Not surprisingly, its metabolism is finely tuned to satisfy growth requirements and in response to nutrient availability. A number of studies have begun to unveil the connections between glucose metabolism and splicing programs. Alternative splicing modulates the ratio between M1 and M2 isoforms of pyruvate kinase in this way determining the choice between aerobic glycolysis and complete glucose oxidation in the Krebs cycle. Reciprocally, intermediates in the Krebs cycle may impact splicing programs at different levels by modulating the activity of 2-oxoglutarate-dependent oxidases. In this review we discuss the molecular mechanisms that coordinate alternative splicing programs with glucose metabolism, two aspects with profound implications in human diseases.
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