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

• Published in: Experimental cell research Vol. 391; no. 1; p. 111973
• Main Authors: Cao, Xiongwen, Slavoff, Sarah A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2020
• Subjects: Codon, Initiator - chemistry; Codon, Initiator - metabolism; Computational Biology - methods; Eukaryota - genetics; Eukaryota - metabolism; Genome; Genomics; High-Throughput Nucleotide Sequencing; Molecular Sequence Annotation - methods; Non-AUG start Codon; Open Reading Frames; Peptide Chain Initiation, Translational; Prokaryotic Cells - metabolism; Protein Sorting Signals - genetics; Proteome - classification; Proteome - genetics; Proteome - metabolism; Proteomics; Ribosomes - classification; Ribosomes - genetics; Ribosomes - metabolism; Small ORF; sORF; Small ORF; sORF; Genomics; Proteomics; Non-AUG start Codon
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2020.111973

Recent ribosome profiling and proteomic studies have revealed the presence of thousands of novel coding sequences, referred to as small open reading frames (sORFs), in prokaryotic and eukaryotic genomes. These genes have defied discovery via traditional genomic tools not only because they tend to be shorter than standard gene annotation length cutoffs, but also because they are, as a class, enriched in sequence properties previously assumed to be unusual, including non-AUG start codons. In this review, we summarize what is currently known about the incidence, efficiency, and mechanism of non-AUG start codon usage in prokaryotes and eukaryotes, and provide examples of regulatory and functional sORFs that initiate at non-AUG codons. While only a handful of non-AUG-initiated novel genes have been characterized in detail to date, their participation in important biological processes suggests that an improved understanding of this class of genes is needed.