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GENE REGULATION

The functions of short ORFs and their microproteins

Nature Reviews Molecular Cell Biology volume 21, pages 252–253 (2020)Cite this article

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The annotation of open reading frames (ORFs) is based on sequence features, and many ORFs are in fact not coding sequences (CDSs) as they do not undergo translation. Furthermore, most short ORFs are not annotated and it is not generally known whether they are CDSs and whether the translated peptides are functional. Chen et al. now report the systematic identification of short CDSs and the characterization of peptides or microproteins they encode in the human genome.

The expression of hundreds of non-canonical CDS peptides was confirmed by mass-spectroscopy-based proteomics and by antigen peptidomics. To test the functionality of the thousands of non-canonical CDSs, their importance for cell growth was tested by CRISPR–Cas9-medited genomic CDS deletion screens in different human cell types. Hundreds of knockouts significantly affected cell growth, including protein variant, start overlap, uORF and lncRNA CDS knockouts; many affected growth in different cell types, indicating they have housekeeping roles. The effects of some uORFs could be in part mediated by the peptides they encode and not by translation deregulation of downstream ORFs.

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References

Original article

  • Chen, J. et al. Pervasive functional translation of noncanonical human open reading frames. Science 367, 1140–1146 (2020)

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Related article

  • Couso, J.-P. & Patraquim, P. Classification and function of small open reading frames. Nat. Rev. Mol. Cell Biol. 18, 575–589 (2017)

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  1. Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/

    Eytan Zlotorynski

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  1. Eytan Zlotorynski
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Correspondence to Eytan Zlotorynski.

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Zlotorynski, E. The functions of short ORFs and their microproteins. Nat Rev Mol Cell Biol 21, 252–253 (2020). https://doi.org/10.1038/s41580-020-0239-7

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  • DOI: https://doi.org/10.1038/s41580-020-0239-7

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