Eukaryotic Microproteins

Microproteins are polypeptides of 100–150 amino acids or fewer that have not been annotated by genome annotation consortia, given their small size and other noncanonical properties. Translated microproteins are now known to number in the thousands in the human genome, to function in critical cellular and physiological processes, and to be dysregulated or mutated in diseases including neurodegeneration and cancer. Knowledge about microproteins has rapidly accumulated since the advent of ribosome profiling enabled their global discovery 15 years ago. In this review, we summarize what is known about eukaryotic microprotein discovery, the sequences and expression mechanisms of small open reading frames, and microprotein functions from yeast to human.