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Front. Oncol. | doi: 10.3389/fonc.2018.00408

The Krebs Cycle Connection: Reciprocal Influence between Alternative Splicing Programs and Cell Metabolism

  • 1Istituto di Genetica Molecolare CNR, Italy

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.

Keywords: splicing regulation, Histone Modifications, Piruvate kinase, 2-OG, 2-oxoglutarate, KDM, Lysine Demethylase, m6A demethylase, DNA demethylases (TETs)

Received: 13 Jun 2018; Accepted: 06 Sep 2018.

Edited by:

Michael Eccles, University of Otago, New Zealand

Reviewed by:

Massimo Broggini, Istituto Di Ricerche Farmacologiche Mario Negri, Italy
Tania L. Slatter, University of Otago, New Zealand
Rotem Karni, Hebrew University of Jerusalem, Israel  

Copyright: © 2018 Biamonti, Maita and Montecucco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Giuseppe Biamonti, Istituto di Genetica Molecolare CNR, Pavia, Lombardy, Italy,
Dr. Alessandra Montecucco, Istituto di Genetica Molecolare CNR, Pavia, Lombardy, Italy,