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Updated: May 11, 2025
An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Eukaryotic Microproteins
Nadiya Jaunbocus1,2, Valerie Ebenki1,2, Haomiao Su1,2
1Department of Chemistry, Yale University, New Haven, Connecticut, USA;
Abstract:
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.
Insights
Microproteins, small proteins missed by genome annotation, are numerous and vital in human cells. Their discovery and functions in health and disease are rapidly advancing.
Area of Science:
- Biochemistry and Molecular Biology
- Genomics
- Cellular Biology
Background:
- Microproteins are small polypeptides (<150 amino acids) often missed by traditional genome annotation due to their size and properties.
- Thousands of microproteins are translated from the human genome, playing roles in essential cellular and physiological functions.
- Dysregulation or mutation of microproteins is implicated in diseases like neurodegeneration and cancer.
Purpose of the Study:
- To review the current knowledge on eukaryotic microprotein discovery.
- To summarize the characteristics of small open reading frames (sORFs) and their expression.
- To discuss the known functions of microproteins across different species, from yeast to humans.
Main Methods:
- Review of existing literature and recent advancements in the field of microprotein research.
- Focus on discoveries enabled by ribosome profiling techniques.
- Synthesis of information regarding sequence, expression, and functional data.
Main Results:
- Global discovery of microproteins has accelerated significantly in the last 15 years.
- Microproteins are involved in critical cellular pathways and physiological processes.
- Evidence links microprotein dysregulation to various human diseases.
Conclusions:
- Microproteins represent a significant and functionally important class of proteins.
- Continued research into microproteins is crucial for understanding fundamental biology and disease mechanisms.
- The field of microprotein research is dynamic and rapidly expanding.
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