@article{945b7729da9646769236603a15481f33,
title = "A high-resolution map of human RNA translation",
abstract = "Translated small open reading frames (smORFs) can have important regulatory roles and encode microproteins, yet their genome-wide identification has been challenging. We determined the ribosome locations across six primary human cell types and five tissues and detected 7,767 smORFs with translational profiles matching those of known proteins. The human genome was found to contain highly cell-type- and tissue-specific smORFs and a subset that encodes highly conserved amino acid sequences. Changes in the translational efficiency of upstream-encoded smORFs (uORFs) and the corresponding main ORFs predominantly occur in the same direction. Integration with 456 mass-spectrometry datasets confirms the presence of 603 small peptides at the protein level in humans and provides insights into the subcellular localization of these small proteins. This study provides a comprehensive atlas of high-confidence translated smORFs derived from primary human cells and tissues in order to provide a more complete understanding of the translated human genome.",
keywords = "dORFs, lncRNAs, Ribo-seq, Ribosome profiling, smORFs, translation, untranslated regions, uORFs",
author = "Chothani, \{Sonia P.\} and Eleonora Adami and Widjaja, \{Anissa A.\} and Langley, \{Sarah R.\} and Sivakumar Viswanathan and Pua, \{Chee Jian\} and Zhihao, \{Nevin Tham\} and Nathan Harmston and Giuseppe D'Agostino and Nicola Whiffin and Wang Mao and Ouyang, \{John F.\} and Lim, \{Wei Wen\} and Shiqi Lim and Lee, \{Cheryl Q.E.\} and Alexandra Grubman and Joseph Chen and Kovalik, \{J. P.\} and Karl Tryggvason and Polo, \{Jose M.\} and Lena Ho and Cook, \{Stuart A.\} and Rackham, \{Owen J.L.\} and Sebastian Schafer",
note = "Funding Information: We thank Dr. Dennis Kappei for providing expert feedback on proteomics analysis. This work was supported by the Open Fund -Young Individual Research Grant (OFYIRG18nov-0014), Duke-NUS-GCR/2018/0017A Grant, and the Academic Clinical Programme Charles Toh Cardiovascular Fellowship Award to S. Schafer. The work was also supported by a Singapore National Research Foundation (NRF) Competitive Research Programme (CRP) grant (NRF-CRP20-2017-0002) and National Medical Research Council (NMRC) Young Investigators Research Grant (YIRG) (NMRC/OFYIRG/0022/2016) awarded to O. Rackham. L.H. is supported by NRF-NRFF2017-05 and HHMI IRSP 55008732. O.J.L.R. S.A.C. and S.S. conceived and arranged funding for the study. O.J.L.R. and S.S. designed and managed the implementation of the study. S.P.C. E.A. O.J.L.R. and S.S. wrote the manuscript with input from coauthors. S.P.C. performed data processing, Ribo-seq analysis, and pipeline development and implementation. E.A. performed and organized the molecular biology experiments. S.P.C. and E.A. created the visualization of results. S.L. A.A.W. S.V. W.M. and W.W.L. assisted in molecular biology experiments and in vitro cell culture. S.R.L. and N.T.Z. assisted with mass spec analysis. G.D. J.F.O. and N.H. performed aspects of the data processing and N.H. provided guidance for the evolutionary analysis. N.W. assisted in the manuscript preparation and genetic aspects of the Ribo-seq analysis. C.J.P. assisted with sequencing. J.M.P. C.Q.E.L. A.G. J.C. J.P.K. and K.T. provided samples collection and expertise in cell culture. L.H. provided in-depth feedback during the manuscript preparation and provided expertise in smORF detection. Having provided an equal contribution toward this work, the first and senior authors are listed in an arbitrary order. S.S. and S.A.C. are co-founders and shareholders of Enleofen Bio Pte Ltd. O.J.L.R. and J.M.P. are SAB members and shareholders of Mogrify Ltd. All other authors declare no competing interests. Funding Information: We thank Dr. Dennis Kappei for providing expert feedback on proteomics analysis. This work was supported by the Open Fund -Young Individual Research Grant ( OFYIRG18nov-0014 ), Duke-NUS-GCR/2018/0017A Grant, and the Academic Clinical Programme Charles Toh Cardiovascular Fellowship Award to S. Schafer. The work was also supported by a Singapore National Research Foundation (NRF) Competitive Research Programme (CRP) grant ( NRF-CRP20-2017-0002 ) and National Medical Research Council (NMRC) Young Investigators Research Grant (YIRG) ( NMRC/OFYIRG/0022/2016 ) awarded to O. Rackham. L.H. is supported by NRF-NRFF2017-05 and HHMI IRSP 55008732 . Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = aug,
day = "4",
doi = "10.1016/j.molcel.2022.06.023",
language = "English",
volume = "82",
pages = "2885--2899.e8",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Elsevier",
number = "15",
}