Pervasive functional translation of noncanonical human open reading frames.

Science
Jin ChenJonathan S Weissman

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.

References

Aug 1, 1997·Genome Research·M A BasraiJ D Boeke
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·David H MacLennan, Evangelia G Kranias
Jul 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Krishna M Vattem, Ronald C Wek
Apr 22, 2011·EMBO Reports·Catherine S PalmerMichael T Ryan
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xiaojun LianSean P Palecek
Nov 20, 2012·Nature Chemical Biology·Sarah A SlavoffAlan Saghatelian
Nov 28, 2012·Science·Noam Stern-GinossarJonathan S Weissman
Dec 3, 2013·The Journal of Biological Chemistry·Chien-fei LeeYijuang Chern
Dec 18, 2013·Science·Tim WangEric S Lander
Jan 11, 2014·Science·Andrea PauliAlexander F Schier
Mar 13, 2014·The Journal of Biological Chemistry·Sarah A SlavoffAlan Saghatelian
Aug 28, 2014·Cell Reports·Nicholas T IngoliaJonathan S Weissman
Oct 14, 2014·Cell·Luke A GilbertJonathan S Weissman
Jan 20, 2015·Nature Genetics·Matthew K IyerArul M Chinnaiyan
Jun 13, 2015·Genome Research·Han XuX Shirley Liu
Jun 30, 2015·Nature Methods·Bastian LinderSamie R Jaffrey
Jan 19, 2016·Nature Biotechnology·John G DoenchDavid E Root
Feb 21, 2016·The EMBO Journal·Timothy G JohnstoneAntonio J Giraldez
Mar 15, 2016·Cell Stem Cell·Mohammad A MandegarBruce R Conklin
May 25, 2016·Nature Communications·Guo-Liang ChewAlexander F Schier
Jun 9, 2016·Proceedings of the National Academy of Sciences of the United States of America·Manuel D LeonettiBo Huang
Nov 4, 2016·Nature Protocols·Stefka TyanovaJuergen Cox
Nov 24, 2016·BMC Genomics·Joshua G Dunn, Jonathan S Weissman
Dec 6, 2016·Nature Chemical Biology·Nadia G D'LimaSarah A Slavoff
Dec 27, 2016·Nature·Akinobu MatsumotoPier Paolo Pandolfi
Jan 13, 2017·Nature·Ataman SendoelElaine Fuchs

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Citations

Jul 3, 2020·Médecine sciences : M/S·Bertrand Jordan
Jul 24, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Jacob B Pierce, Mark W Feinberg
Aug 4, 2020·The EMBO Journal·Samantha Dodbele, Jeremy E Wilusz
Jun 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aaron J W Hsueh, Yi Feng
Aug 11, 2020·American Journal of Physiology. Endocrinology and Metabolism·Troy L MerryChanghan Lee
Sep 2, 2020·Wiley Interdisciplinary Reviews. RNA·Christina Akirtava, Charles Joel McManus
Aug 12, 2020·Current Protocols in Bioinformatics·Marie A BrunetXavier Roucou
Aug 21, 2020·Nature Reviews. Immunology·Devin DershJonathan W Yewdell
Jul 31, 2020·Genome Biology·Marco PreussnerFlorian Heyd
Apr 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·James D Phelan, Louis M Staudt
Mar 27, 2020·Nature Reviews. Molecular Cell Biology·Eytan Zlotorynski
Sep 17, 2020·Cancers·Anca ApavaloaeiClaude Perreault
Mar 7, 2020·Science·Lian-Huan Wei, Junjie U Guo
Oct 6, 2020·Frontiers in Plant Science·Xiaoyu YangLin Liu
Jul 19, 2020·Human Molecular Genetics·Deivid Carvalho RodriguesJames Ellis
Oct 24, 2020·ELife·Tamer Ali, Phillip Grote
Nov 4, 2020·RNA Biology·Katharina Walther, Leon N Schulte
Nov 17, 2020·Wiley Interdisciplinary Reviews. RNA·Sara J Johnson, Thomas A Cooper
Sep 2, 2020·Annual Review of Genetics·Thomas E DeverMatthew S Sachs
Jul 4, 2020·Cancer Research·A Rouf BandayLudmila Prokunina-Olsson
Nov 3, 2020·Computational and Structural Biotechnology Journal·Sebastien Leblanc, Marie A Brunet
Jan 20, 2021·The Journal of Cell Biology·Mary Catherine BridgesAntonis Kourtidis
Aug 2, 2020·Seminars in Cancer Biology·Ammad Ahmad FarooqiMassimo Mallardo
Dec 3, 2020·Cancer Immunology Research·Edward F FritschCatherine J Wu
Jan 23, 2021·Nature Communications·Xiongwen CaoSarah A Slavoff
Feb 9, 2021·Nucleic Acids Research·Agnes KarasikNicholas R Guydosh
Nov 29, 2020·Trends in Biochemical Sciences·Tristan CardonMichel Salzet
Dec 18, 2020·Frontiers in Genetics·Marina AznaourovaLeon N Schulte
Dec 11, 2020·Scientific Reports·Shraddha PuntambekarSudhakaran Prabakaran
Dec 23, 2020·International Journal of Molecular Sciences·Karen S Kim GuisbertEric Guisbert
Oct 23, 2020·Cancer Cell International·Mujie YeKuiran Dong
Oct 30, 2020·Cancers·Cong Zhou, Shiwei Duan
Nov 13, 2020·Nucleic Acids Research·Marie A BrunetXavier Roucou
Feb 19, 2021·Nature Communications·Hong ZhangJian Lu

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