Pervasive functional translation of noncanonical human open reading frames

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Pervasive functional translation of noncanonical human open reading frames. / 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.

In: Science, Vol. 367, No. 6482, 2020, p. 1140-1146.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Chen, J, Brunner, A-D, Cogan, JZ, Nuñez, JK, Fields, AP, Adamson, B, Itzhak, DN, Li, JY, Mann, M, Leonetti, MD & Weissman, JS 2020, 'Pervasive functional translation of noncanonical human open reading frames', Science, vol. 367, no. 6482, pp. 1140-1146. https://doi.org/10.1126/science.aay0262

APA

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), 1140-1146. https://doi.org/10.1126/science.aay0262

Vancouver

Chen J, Brunner A-D, Cogan JZ, Nuñez JK, Fields AP, Adamson B et al. Pervasive functional translation of noncanonical human open reading frames. Science. 2020;367(6482):1140-1146. https://doi.org/10.1126/science.aay0262

Author

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. / Pervasive functional translation of noncanonical human open reading frames. In: Science. 2020 ; Vol. 367, No. 6482. pp. 1140-1146.

Bibtex

@article{169ea8b4a20847dbbeffa1e729955a09,
title = "Pervasive functional translation of noncanonical human open reading frames",
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.",
keywords = "CRISPR-Cas Systems, Humans, Open Reading Frames, Operon, Peptides/genetics, Protein Biosynthesis/genetics, RNA, Messenger/genetics, Ribosomes/metabolism, Transcriptome",
author = "Jin Chen and Andreas-David Brunner and Cogan, {J Zachery} and Nu{\~n}ez, {James K} and Fields, {Alexander P} and Britt Adamson and Itzhak, {Daniel N} and Li, {Jason Y} and Matthias Mann and Leonetti, {Manuel D} and Weissman, {Jonathan S}",
year = "2020",
doi = "10.1126/science.aay0262",
language = "English",
volume = "367",
pages = "1140--1146",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6482",

}

RIS

TY - JOUR

T1 - Pervasive functional translation of noncanonical human open reading frames

AU - Chen, Jin

AU - Brunner, Andreas-David

AU - Cogan, J Zachery

AU - Nuñez, James K

AU - Fields, Alexander P

AU - Adamson, Britt

AU - Itzhak, Daniel N

AU - Li, Jason Y

AU - Mann, Matthias

AU - Leonetti, Manuel D

AU - Weissman, Jonathan S

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - CRISPR-Cas Systems

KW - Humans

KW - Open Reading Frames

KW - Operon

KW - Peptides/genetics

KW - Protein Biosynthesis/genetics

KW - RNA, Messenger/genetics

KW - Ribosomes/metabolism

KW - Transcriptome

U2 - 10.1126/science.aay0262

DO - 10.1126/science.aay0262

M3 - Journal article

C2 - 32139545

VL - 367

SP - 1140

EP - 1146

JO - Science

JF - Science

SN - 0036-8075

IS - 6482

ER -

ID: 239206401