Microproteins: Overlooked regulators of physiology and disease

Keira R Hassel; Omar Brito-Estrada; Catherine A Makarewich

doi:10.1016/j.isci.2023.106781

Microproteins: Overlooked regulators of physiology and disease

iScience. 2023 Apr 29;26(6):106781. doi: 10.1016/j.isci.2023.106781. eCollection 2023 Jun 16.

Authors

Keira R Hassel^{1

2}, Omar Brito-Estrada^{1

2}, Catherine A Makarewich^{1

3}

Affiliations

¹ The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
² University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.

Abstract

Ongoing efforts to generate a complete and accurate annotation of the genome have revealed a significant blind spot for small proteins (<100 amino acids) originating from short open reading frames (sORFs). The recent discovery of numerous sORF-encoded proteins, termed microproteins, that play diverse roles in critical cellular processes has ignited the field of microprotein biology. Large-scale efforts are currently underway to identify sORF-encoded microproteins in diverse cell-types and tissues and specialized methods and tools have been developed to aid in their discovery, validation, and functional characterization. Microproteins that have been identified thus far play important roles in fundamental processes including ion transport, oxidative phosphorylation, and stress signaling. In this review, we discuss the optimized tools available for microprotein discovery and validation, summarize the biological functions of numerous microproteins, outline the promise for developing microproteins as therapeutic targets, and look forward to the future of the field of microprotein biology.

Keywords: Biochemistry; Biological sciences; Cell biology; Molecular biology.

Publication types

Review

Abstract

Publication types

Grants and funding