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A high-resolution map of human RNA translation

A high-resolution map of human RNA translation
A high-resolution map of human RNA translation

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.

Ribo-seq, Ribosome profiling, dORFs, lncRNAs, smORFs, translation, uORFs, untranslated regions
1097-2765
2885-2899.e8
Chothani, Sonia P.
8d64ecf3-6918-446a-997a-e0f14ef1a974
Adami, Eleonora
c68076ed-059b-4f12-bb41-22f55de4cbae
Widjaja, Anissa A.
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Langley, Sarah R.
897e76ce-ff32-43dc-abe6-6b347bad7fd1
Viswanathan, Sivakumar
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Pua, Chee Jian
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Zhihao, Nevin Tham
075dcd8f-947d-4ac9-80c8-fe004bb34c0a
Harmston, Nathan
017e019d-7784-4ed4-a4d9-38880f08df3f
D’agostino, Giuseppe
dae9770f-b48c-48f5-b898-5483fef65cb9
Whiffin, Nicola
a12b021c-3330-4a73-9dc2-dea3d79ba9a8
Mao, Wang
72f137cb-48d1-419c-b8a5-46ff38f197d0
Ouyang, John F.
ce6f93a5-b40f-4add-8d7b-3ae795c1a4cb
Lim, Wei Wen
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Lim, Shiqi
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Lee, Cheryl Q.e.
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Grubman, Alexandra
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Chen, Joseph
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Kovalik, J.p.
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Tryggvason, Karl
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Polo, Jose M.
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Ho, Lena
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Cook, Stuart A.
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Rackham, Owen J.l.
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
Schafer, Sebastian
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Chothani, Sonia P.
8d64ecf3-6918-446a-997a-e0f14ef1a974
Adami, Eleonora
c68076ed-059b-4f12-bb41-22f55de4cbae
Widjaja, Anissa A.
11120825-c28e-4fe6-9831-8602ff1651d0
Langley, Sarah R.
897e76ce-ff32-43dc-abe6-6b347bad7fd1
Viswanathan, Sivakumar
3a7c01b3-ebb9-4329-96a6-f1b111a8a765
Pua, Chee Jian
b4bda66c-ff80-48f7-b6a6-45c094e09420
Zhihao, Nevin Tham
075dcd8f-947d-4ac9-80c8-fe004bb34c0a
Harmston, Nathan
017e019d-7784-4ed4-a4d9-38880f08df3f
D’agostino, Giuseppe
dae9770f-b48c-48f5-b898-5483fef65cb9
Whiffin, Nicola
a12b021c-3330-4a73-9dc2-dea3d79ba9a8
Mao, Wang
72f137cb-48d1-419c-b8a5-46ff38f197d0
Ouyang, John F.
ce6f93a5-b40f-4add-8d7b-3ae795c1a4cb
Lim, Wei Wen
2577d8b6-57ea-4bd3-b607-a46ca716fc1b
Lim, Shiqi
abd52ba6-8bbc-456b-8626-f4d2e4e79a68
Lee, Cheryl Q.e.
63ff4b10-b7ed-4a50-ab6e-3bc8b1c91b8e
Grubman, Alexandra
f441d27d-645c-4c8f-8cd1-64f5fece12e8
Chen, Joseph
366c5516-4ae2-4431-b641-47fc1f3941ff
Kovalik, J.p.
d412c6ec-2e4d-4a0e-b392-c61159deef1f
Tryggvason, Karl
0f60be6a-0f0c-4dbe-8823-baa1971a96b9
Polo, Jose M.
f55d7039-bd9e-4e56-98e3-fdf3d118d4f3
Ho, Lena
af551935-bac5-441a-8f6c-9eaefd20cb7a
Cook, Stuart A.
2c9730f9-0c9b-4d81-a32b-2fa1180b8153
Rackham, Owen J.l.
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
Schafer, Sebastian
6946786d-17c8-4c35-a6ac-871cc7a82cf2

Chothani, Sonia P., Adami, Eleonora, Widjaja, Anissa A., Langley, Sarah R., Viswanathan, Sivakumar, Pua, Chee Jian, Zhihao, Nevin Tham, Harmston, Nathan, D’agostino, Giuseppe, Whiffin, Nicola, Mao, Wang, Ouyang, John F., Lim, Wei Wen, Lim, Shiqi, Lee, Cheryl Q.e., Grubman, Alexandra, Chen, Joseph, Kovalik, J.p., Tryggvason, Karl, Polo, Jose M., Ho, Lena, Cook, Stuart A., Rackham, Owen J.l. and Schafer, Sebastian (2022) A high-resolution map of human RNA translation. Molecular Cell, 82 (15), 2885-2899.e8. (doi:10.1016/j.molcel.2022.06.023).

Record type: Article

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.

Text
ChothaniEtAl_2022 - Accepted Manuscript
Restricted to Repository staff only until 15 July 2023.
Available under License Creative Commons Attribution Non-commercial No Derivatives.
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More information

Accepted/In Press date: 15 June 2022
e-pub ahead of print date: 15 July 2022
Published date: 4 August 2022
Related URLs:
Keywords: Ribo-seq, Ribosome profiling, dORFs, lncRNAs, smORFs, translation, uORFs, untranslated regions
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Identifiers

Local EPrints ID: 469988
URI: http://eprints.soton.ac.uk/id/eprint/469988
DOI: doi:10.1016/j.molcel.2022.06.023
ISSN: 1097-2765
PURE UUID: c25ad0ae-0cf0-41ff-9101-8038f1ae8e34
ORCID for Owen J.l. Rackham: ORCID iD orcid.org/0000-0002-4390-0872

Catalogue record

Date deposited: 29 Sep 2022 16:48
Last modified: 30 Sep 2022 02:01

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Contributors

Author: Sonia P. Chothani
Author: Eleonora Adami
Author: Anissa A. Widjaja
Author: Sarah R. Langley
Author: Sivakumar Viswanathan
Author: Chee Jian Pua
Author: Nevin Tham Zhihao
Author: Nathan Harmston
Author: Giuseppe D’agostino
Author: Nicola Whiffin
Author: Wang Mao
Author: John F. Ouyang
Author: Wei Wen Lim
Author: Shiqi Lim
Author: Cheryl Q.e. Lee
Author: Alexandra Grubman
Author: Joseph Chen
Author: J.p. Kovalik
Author: Karl Tryggvason
Author: Jose M. Polo
Author: Lena Ho
Author: Stuart A. Cook
Author: Owen J.l. Rackham ORCID iD
Author: Sebastian Schafer

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