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Pervasive functional translation of noncanonical human open reading frames

Author(s): Chen, Jin; Brunner, Andreas-David; Cogan, J Zachery; Nuñez, James K; Fields, Alexander P; et al

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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.
Publication Date: 6-Mar-2020
Citation: Chen, Jin, Brunner, Andreas-David, Cogan, J Zachery, Nuñez, James K, Fields, Alexander P, Adamson, Britt, Itzhak, Daniel N, Li, Jason Y, Mann, Matthias, Leonetti, Manuel D, Weissman, Jonathan S. (2020). Pervasive functional translation of noncanonical human open reading frames. Science, 367 (6482), 1140 - 1146. doi:10.1126/science.aay0262
DOI: doi:10.1126/science.aay0262
ISSN: 0036-8075
EISSN: 1095-9203
Pages: 1140 - 1146
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Science
Version: Author's manuscript

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