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  Pervasive functional translation of noncanonical human open reading frames

Chen, J., Brunner, A.-D., Cogan, J. Z., Nunez, J. K., Fields, A. P., Adamson, B., et al. (2020). Pervasive functional translation of noncanonical human open reading frames. SCIENCE, 367(6482), 1140-+. doi:10.1126/science.aay0262.

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Genre: Journal Article

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 Creators:
Chen, Jin1, Author
Brunner, Andreas-David2, Author              
Cogan, J. Zachery1, Author
Nunez, James K.1, Author
Fields, Alexander P.1, Author
Adamson, Britt1, Author
Itzhak, Daniel N.1, Author
Li, Jason Y.1, Author
Mann, Matthias2, Author              
Leonetti, Manuel D.1, Author
Weissman, Jonathan S.1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: MASS-SPECTROMETRY; GENETIC SCREENS; NONCODING RNAS; UPSTREAM ORFS; STEM-CELLS; PROTEIN; REVEALS; SINGLE; MICROPEPTIDE; PEPTIDES
 Abstract: Ribosome profiling has revealed pervasive but largely uncharacterized translation outside of canonical coding sequences (CDSs). In this work, we exploit a systematic CRISPR-based screening strategy to identify hundreds of noncanonical CDSs that are essential for cellular growth and whose disruption elicits specific, robust transcriptomic and phenotypic changes in human cells. Functional characterization of the encoded microproteins reveals distinct cellular localizations, specific protein binding partners, and hundreds of microproteins that are presented by the human leukocyte antigen system. We find multiple microproteins encoded in upstream open reading frames, which form stable complexes with the main, canonical protein encoded on the same messenger RNA, thereby revealing the use of functional bicistronic operons in mammals. Together, our results point to a family of functional human microproteins that play critical and diverse cellular roles.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 53
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000520018400044
DOI: 10.1126/science.aay0262
 Degree: -

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Title: SCIENCE
Source Genre: Journal
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Publ. Info: 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA : AMER ASSOC ADVANCEMENT SCIENCE
Pages: - Volume / Issue: 367 (6482) Sequence Number: - Start / End Page: 1140 - + Identifier: ISSN: 0036-8075