Metabolic regulation of mRNA splicing

Haissi Cui; Qingyu Shi; Colette Maya Macarios; Paul Schimmel

doi:10.1016/j.tcb.2024.02.002

Metabolic regulation of mRNA splicing

Trends Cell Biol. 2024 Mar 1:S0962-8924(24)00025-4. doi: 10.1016/j.tcb.2024.02.002. Online ahead of print.

Authors

Haissi Cui¹, Qingyu Shi², Colette Maya Macarios², Paul Schimmel³

Affiliations

¹ Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada. Electronic address: haissi.cui@utoronto.ca.
² Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.
³ Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: schimmel@scripps.edu.

PMID: 38431493
DOI: 10.1016/j.tcb.2024.02.002

Abstract

Alternative mRNA splicing enables the diversification of the proteome from a static genome and confers plasticity and adaptiveness on cells. Although this is often explored in development, where hard-wired programs drive the differentiation and specialization, alternative mRNA splicing also offers a way for cells to react to sudden changes in outside stimuli such as small-molecule metabolites. Fluctuations in metabolite levels and availability in particular convey crucial information to which cells react and adapt. We summarize and highlight findings surrounding the metabolic regulation of mRNA splicing. We discuss the principles underlying the biochemistry and biophysical properties of mRNA splicing, and propose how these could intersect with metabolite levels. Further, we present examples in which metabolites directly influence RNA-binding proteins and splicing factors. We also discuss the interplay between alternative mRNA splicing and metabolite-responsive signaling pathways. We hope to inspire future research to obtain a holistic picture of alternative mRNA splicing in response to metabolic cues.

Keywords: RNA; amino acid; glucose; mRNA splicing; metabolite.

Publication types

Review