Pervasive functional translation of noncanonical human open reading frames

Jin Chen, Andreas David Brunner, J. Zachery Cogan, James K. Nuñez, Alexander P. Fields, Britt Adamson, Daniel N. Itzhak, Jason Y. Li, Matthias Mann, Manuel D. Leonetti, Jonathan S. Weissman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)140-146
Number of pages7
JournalScience
Volume367
Issue number6482
DOIs
StatePublished - Mar 6 2020

All Science Journal Classification (ASJC) codes

  • General

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    Chen, J., Brunner, A. D., Cogan, J. Z., Nuñez, J. K., Fields, A. P., Adamson, B., Itzhak, D. N., Li, J. Y., Mann, M., Leonetti, M. D., & Weissman, J. S. (2020). Pervasive functional translation of noncanonical human open reading frames. Science, 367(6482), 140-146. https://doi.org/10.1126/science.aav5912