sORF

Small open reading frame (sORF) refers to an open reading frame that typically encodes a peptide shorter than about 100 amino acids. sORFs are widespread in genomes and can be located in annotated protein-coding genes, in 5' and 3' untranslated regions, within long noncoding RNAs, or in intergenic sequences. They may produce functional micropeptides involved in muscle function, development, signaling, and metabolism, although many remain uncharacterized.

Detection of sORFs has accelerated with advances in ribosome profiling, which captures actively translating ribosomes, and with proteomics approaches that identify small peptides. Comparative genomics and coding-potential assessment also assist in distinguishing genuine sORFs from random short ORFs. Not all sORFs produce stable or functional peptides; some regulate translation of larger coding sequences or act as regulatory RNAs.

The term sORF is used broadly; a subset called upstream ORFs (uORFs) reside in the 5' UTRs of mRNAs, and downstream ORFs (dORFs) lie in other regions. Across domains, bacteria, archaea, and eukaryotes host sORFs, with examples including micropeptides that regulate signaling and other cellular processes.

Annotation and functional characterization remain incomplete, in part due to the small size and often weak sequence conservation of sORFs. Ongoing improvements in detection methods and functional assays are expected to refine the catalog of sORFs and clarify their biological roles.