A high-resolution map of human RNA translation

Sonia P. Chothani, Eleonora Adami, Anissa A. Widjaja, Sarah R. Langley, Sivakumar Viswanathan, Chee Jian Pua, Nevin Tham Zhihao, Nathan Harmston, Giuseppe D'Agostino, Nicola Whiffin, Wang Mao, John F. Ouyang, Wei Wen Lim, Shiqi Lim, Cheryl Q.E. Lee, Alexandra Grubman, Joseph Chen, J. P. Kovalik, Karl Tryggvason, Jose M. PoloLena Ho, Stuart A. Cook, Owen J.L. Rackham, Sebastian Schafer

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2885-2899.e8
Number of pages24
JournalMolecular Cell
Volume82
Issue number15
DOIs
Publication statusPublished - 4 Aug 2022

Keywords

  • dORFs
  • lncRNAs
  • Ribo-seq
  • Ribosome profiling
  • smORFs
  • translation
  • untranslated regions
  • uORFs

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