Microproteins at the Frontiers of Biology and Medicine

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Microproteins, defined as proteins with fewer than 150 amino acids, represent a newly recognized class of functional genes.
• Historically, gene function was assumed to be limited to large, conserved proteins, a notion challenged by microprotein discoveries.

Purpose of the Study:

• To review the current understanding of microprotein discovery and their biological functions.
• To highlight key examples of microproteins implicated in human diseases.
• To discuss the future opportunities and challenges in microprotein research.

Main Methods:

• Advances in ribosome profiling and proteogenomics have enabled the identification of actively translated small open reading frames.
• Genome-wide functional screens are utilized to assess the biological roles of microproteins.
• Literature review and synthesis of existing research on microprotein function and disease association.

Main Results:

• Thousands of small open reading frames are actively translated, producing functional microproteins.
• Microproteins regulate critical cellular processes including metabolism, immunity, cancer development, and neurodegeneration.
• Dysregulation or mutations in microprotein-encoding genes are linked to various pathophysiological conditions.

Conclusions:

• Microproteins are critical modulators of essential biological processes and represent a significant, previously unrecognized component of the functional proteome.
• The link between the noncanonical proteome (microproteins) and human disease is increasingly evident.
• The field of microprotein research is rapidly evolving, presenting new avenues for understanding health and disease.