Non-AUG start codons: Expanding and regulating the small and alternative ORFeome

Area of Science:

• Genomics and Molecular Biology
• Gene Expression and Regulation

Background:

• Recent advances in ribosome profiling and proteomics have identified thousands of novel coding sequences, termed small open reading frames (sORFs).
• These sORFs are often overlooked by traditional genomic methods due to their short length and unusual sequence properties, such as non-AUG start codons.

Purpose of the Study:

• To review the current knowledge on the prevalence, efficiency, and mechanisms of non-AUG start codon usage in prokaryotes and eukaryotes.
• To highlight functional and regulatory sORFs that initiate translation using non-AUG codons.

Main Methods:

• Review of recent ribosome profiling and proteomic studies.
• Analysis of genomic data for sORF identification and characterization.
• Compilation of known examples of non-AUG-initiated sORFs.

Main Results:

• Thousands of sORFs have been identified across prokaryotic and eukaryotic genomes.
• Non-AUG start codons are frequently utilized by sORFs, a property previously considered unusual.
• Several regulatory and functional sORFs initiating at non-AUG codons have been documented.

Conclusions:

• Non-AUG-initiated sORFs represent a significant, previously underappreciated class of genes.
• Despite limited detailed characterization, these sORFs play roles in vital biological processes.
• Further research is essential to fully understand the scope and impact of non-AUG-initiated sORFs.