Pervasive functional translation of noncanonical human open reading frames
| Autor: | 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 |
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| Rok vydání: | 2020 |
| Předmět: |
General Science & Technology
Prevention 1.1 Normal biological development and functioning Messenger Human Genome Vaccine Related Open Reading Frames Underpinning research Protein Biosynthesis Biodefense Operon Genetics Humans RNA Generic health relevance CRISPR-Cas Systems Peptides Transcriptome Ribosomes Biotechnology |
| Zdroj: | Science (New York, N.Y.), vol 367, iss 6482 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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