PXD014031

PXD014031 is an original dataset announced via ProteomeXchange.

Title	Pervasive functional micropeptides in humans encoded by non-canonical open reading frames
Description	Protein-coding regions of the genome continue to expand beyond canonical annotations and remain incompletely understood. Despite recent reports demonstrating important cellular functions played by micropeptides from unannotated open reading frames (ORFs), there exists no systematic method to fully uncover the prevalence of functional ORFs and their encoded peptides. Here, using ribosome profiling and mass spectrometry based proteomics, we reveal pervasive translation of ORFs previously annotated as non-coding, including those encoded on long non-coding RNAs (lncRNA ORFs) and upstream regions of protein-coding messages (uORFs). Cross-validation of novel ORFs in six different cell lines via HLA peptidomics confirm their allotype-specific MHC receptor presentation and their engagement with the endogenous HLA processing machinery. We further developed systematic CRISPR-based screens to show that hundreds of these ORFs are essential for cellular growth and encode stable, functional peptides that play diverse roles in cells. By tagging with a split-GFP system, we show that many of the peptides have specific cellular localization patterns and form functional protein complexes. We uncovered uORFs encoding stable peptides that interact with the downstream protein encoded on the same mRNA, suggesting possible regulatory or feedback roles from the bicistronic message in addition to the previously assumed role of uORFs in translational repression. Our results uncover functional micropeptides encoded in the human genome with essential roles in diverse biological processes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:55:08.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas-David Brunner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-28 01:44:59	ID requested
1	2020-03-06 01:30:42	announced
2	2020-03-24 00:37:57	announced	2020-03-24: Updated publication reference for PubMed record(s): 32139545.
⏵ 3	2024-10-22 04:55:09	announced	2024-10-22: Updated project metadata.

Chen J, Brunner AD, Cogan JZ, Nu, ñ, ez JK, Fields AP, Adamson B, Itzhak DN, Li JY, Mann M, Leonetti MD, Weissman JS, Pervasive functional translation of noncanonical human open reading frames. Science, 367(6482):1140-1146(2020) [pubmed]

10.1126/science.aay0262;

submitter keyword: novel ORFs, Single cell RNA analysis, CRISPR, Ribosome sequencing,LCMS

Matthias Mann
contact affiliation	Max Planck Institute of Biochemistry, Department for Proteomics and Signal transduction
contact email	mmann@biochem.mpg.de
lab head
Andreas-David Brunner
contact affiliation	MAX PLANCK INSTITUTE OF BIOCHEMISTRY
contact email	abrunner@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/03/PXD014031

PRIDE project URI

• PRIDE
  1. PXD014031
     1. Label: PRIDE project
     2. Name: Pervasive functional micropeptides in humans encoded by non-canonical open reading frames