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Classification and function of small open reading frames
journal contribution
posted on 2023-06-09, 12:27 authored by Juan Pablo Couso, Pedro PatraquimSmall open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We propose the existence of several functional classes of smORFs, ranging from inert DNA sequences to transcribed and translated cis-regulators of translation and peptides with a propensity to function as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm. We suggest that the different smORF classes could represent steps in gene, peptide and protein evolution. Our analysis introduces a distinction between different peptide-coding classes of smORFs in animal genomes, and highlights the role of model organisms for the study of small peptide biology in the context of development, physiology and human disease.
Funding
Molecular and cellular functions of membrane peptides encoded by small ORFs; G1791; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/N001753/1
History
Publication status
- Published
Journal
Classification and Function of small Open Reading FramesISSN
1471-0080Publisher
Nature Reviews Molecular Cell BiologyExternal DOI
Volume
18Page range
575-589Department affiliated with
- BSMS Publications
Research groups affiliated with
- climate@sussex Publications
Full text available
- Yes
Peer reviewed?
- Yes