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Classification and function of small open reading frames
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Classification and function of small open reading frames
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Classification and function of small open reading frames
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Journal Article
Classification and function of small open reading frames
2017
Overview
Key Points
Small peptides of 100 amino acids or fewer are encoded by small open reading frames (smORFs) and mediate key physiological functions in animals and humans.
smORFs constitute 99% of transcribed, but only 1% of annotated, coding sequences in flies, mice and humans.
Different smORF classes show distinctive and predictive markers of functionality at the RNA level and the protein sequence level.
The characteristics of different smORF classes are evolutionarily conserved across animal species, encouraging the use of
Drosophila melanogaster
and
Mus musculus
as model organisms for studies of peptide biology in the context of development, physiology and disease.
Different smORF classes may represent steps in the origin and evolution of new genes and proteins.
A comprehensive analysis of small open reading frames (smORFs) in flies, mice and humans supports their classification into different functional groups, from inert DNA sequences to transcribed and translated smORFs that have various activities. The different smORF classes could represent steps in gene, peptide and protein evolution.
Small 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.
