What Can Ribo-Seq, Immunopeptidomics, and Proteomics Tell Us About the Noncanonical Proteome?

John R. Prensner, Jennifer G. Abelin, Leron W. Kok, Karl R. Clauser, Jonathan M. Mudge, Jorge Ruiz-Orera, Michal Bassani-Sternberg, Robert L. Moritz, Eric W. Deutsch, Sebastiaan van Heesch

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

25 Citations (Scopus)

Résumé

Ribosome profiling (Ribo-Seq) has proven transformative for our understanding of the human genome and proteome by illuminating thousands of noncanonical sites of ribosome translation outside the currently annotated coding sequences (CDSs). A conservative estimate suggests that at least 7000 noncanonical ORFs are translated, which, at first glance, has the potential to expand the number of human protein CDSs by 30%, from ∼19,500 annotated CDSs to over 26,000 annotated CDSs. Yet, additional scrutiny of these ORFs has raised numerous questions about what fraction of them truly produce a protein product and what fraction of those can be understood as proteins according to conventional understanding of the term. Adding further complication is the fact that published estimates of noncanonical ORFs vary widely by around 30-fold, from several thousand to several hundred thousand. The summation of this research has left the genomics and proteomics communities both excited by the prospect of new coding regions in the human genome but searching for guidance on how to proceed. Here, we discuss the current state of noncanonical ORF research, databases, and interpretation, focusing on how to assess whether a given ORF can be said to be "protein coding."

langue originaleAnglais
Numéro d'article100631
journalMolecular and Cellular Proteomics
Volume22
Numéro de publication9
Les DOIs
étatPublié - 1 sept. 2023
Modification externeOui

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