Revisiting sORFs: overcoming challenges to identify and characterize functional microproteins

Area of Science:

• Genomics and Proteomics
• Molecular Biology
• Biochemistry

Background:

• Short open reading frames (sORFs) are abundant but often overlooked for their coding potential.
• Functional microproteins (<100 amino acids) are known, yet their discovery from sORFs is challenging.
• Thousands of likely coding sORFs have been identified through recent technological advancements.

Purpose of the Study:

• To provide an overview of the expanding field of microproteins, with a focus on eukaryotic small proteins.
• To discuss emerging themes in the molecular mechanisms of microproteins.
• To highlight advances and challenges in identifying and characterizing microproteins.

Main Methods:

• Ribosome profiling
• Mass spectrometry
• Bioinformatic predictions

Main Results:

• Identification of thousands of putatively coding sORFs.
• Characterization of a subset of microproteins revealing versatile and essential cellular functions.
• Growing evidence for a vast, undiscovered repertoire of microproteins encoded in genomes.

Conclusions:

• Microproteins encoded by sORFs represent a significant and largely unexplored area of biology.
• Technological progress is rapidly advancing the identification and functional characterization of microproteins.
• Further research is crucial to uncover the full scope and importance of microproteins in cellular processes.