Protein Crotonylation Expert Review: A New Lens to Take Post-Translational Modifications and Cell Biology to New Heights.

Abstract

Genome regulation, temporal and spatial variations in cell function, continues to puzzle and interest life scientists who aim to unravel the molecular basis of human health and disease, not to mention plant biology and ecosystem diversity. Despite important advances in epigenomics and protein post-translational modifications over the past decade, there is a need for new conceptual lenses to understand biological mechanisms that can help unravel the fundamental regulatory questions in genomes and the cell. To these ends, lys crotonylation (Kcr) is a reversible protein modification catalyzed by protein crotonyl transferases and decrotonylases. First identified on histones, Kcr regulates cellular processes at the chromatin level. Research thus far has revealed that Kcr marks promoter sites of active genes and potential enhancers. Eventually, Kcr on a number of nonhistone proteins was reported. The abundance of Kcr on ribosomal and myofilament proteins indicates its functional roles in protein synthesis and muscle contraction. Kcr has also been associated with pluripotency, spermiogenesis, and DNA repair. In plants, large-scale mass spectrometry-based experiments validated the roles of Kcr in photosynthesis. In this expert review, we present the latest thinking and findings on lys crotonylation with an eye to regulation of cell biology. We discuss the enrichment techniques, putative biological functions, and challenges associated with studying this protein modification with vast biological implications. Finally, we reflect on the future outlook about the broader relevance of Kcr in animals, microbes, and plant species.