Pervasive functional translation of noncanonical human open reading frames.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
06 03 2020
06 03 2020
Historique:
received:
26
05
2019
revised:
22
11
2019
accepted:
13
01
2020
entrez:
7
3
2020
pubmed:
7
3
2020
medline:
20
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32139545
pii: 367/6482/1140
doi: 10.1126/science.aay0262
pmc: PMC7289059
mid: NIHMS1590480
doi:
Substances chimiques
Peptides
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1140-1146Subventions
Organisme : NIGMS NIH HHS
ID : K99 GM134154
Pays : United States
Organisme : NIGMS NIH HHS
ID : R00 GM134154
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG009490
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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