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.
I: Science, Bind 367, Nr. 6482, 2020, s. 1140-1146.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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