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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_FC2F4DA59A98
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
What Can Ribo-Seq, Immunopeptidomics, and Proteomics Tell Us About the Noncanonical Proteome?
Journal
Molecular & cellular proteomics
Author(s)
Prensner J.R., Abelin J.G., Kok L.W., Clauser K.R., Mudge J.M., Ruiz-Orera J., Bassani-Sternberg M., Moritz R.L., Deutsch E.W., van Heesch S.
ISSN
1535-9484 (Electronic)
ISSN-L
1535-9476
Publication state
Published
Issued date
09/2023
Peer-reviewed
Oui
Volume
22
Number
9
Pages
100631
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
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."
Keywords
Humans, Proteome/metabolism, Protein Biosynthesis, Proteomics/methods, Ribosome Profiling, Ribosomes/metabolism, Open Reading Frames, Ribo-Seq, immunopeptidomics, mass spectrometry, microprotein, noncanonical ORF
Pubmed
Open Access
Yes
Create date
21/08/2023 8:52
Last modification date
23/01/2024 8:37
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