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 - 2020/3/6
Y1 - 2020/3/6
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.
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U2 - 10.1126/science.aay0262
DO - 10.1126/science.aay0262
M3 - Article
C2 - 32139545
SN - 0036-8075
VL - 367
SP - 1140
EP - 1146
JO - Science (New York, N.Y.)
JF - Science (New York, N.Y.)
IS - 6482
ER -