Emerging regulators of human physiology and disease; sORF-encoded microproteins.

Narrative review

“This narrative review summarizes current knowledge regarding the classification, discovery, translational regulation, and biological significance of sORF-encoded microproteins.”

sORF-encoded microproteins in human physiology and disease

“Increasing evidence demonstrates that these molecules play critical regulatory roles in human physiology and disease.”

Expression is controlled by epigenetic and epitranscriptomic mechanisms

“Their expression is tightly controlled by epigenetic mechanisms, including DNA methylation, Polycomb-mediated H3K27 trimethylation, and bivalent histone modifications, as well as epitranscriptomic regulation through N6-methyladenosine-mediated translation.”

Microproteins have diverse roles in cardiometabolic disease, neurodegeneration, and cancer

“Key microproteins such as Humanin, MOTS-c, Myoregulin, DWORF, HOXB-AS3-p, Mitoregulin, and CASIMO1 illustrate the diverse roles of sORF-derived peptides in cardiometabolic disease, neurodegeneration, and cancer.”

The microproteome represents an epigenetically integrated regulatory layer

“Collectively, the sORF-encoded microproteome represents an epigenetically integrated and functionally significant regulatory layer of the human proteome with major implications for fundamental biology and precision medicine.”