RT Journal Article
SR Electronic
T1 InteractORF, predictions of human sORF functions from an interactome study
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.06.10.598216
DO 10.1101/2024.06.10.598216
A1 Slivak, Mathilde
A1 Choteau, Sébastien A.
A1 Pierre, Philippe
A1 Spinelli, Lionel
A1 Zanzoni, Andreas
A1 Brun, Christine
YR 2024
UL http://biorxiv.org/content/early/2024/06/11/2024.06.10.598216.abstract
AB Short Open Reading Frames (sORFs) are ubiquitous genomic elements that have been overlooked for years, essentially due to their short length (< 100 residues) and the use of alternative start codons (other than AUG). However, some may encode functional peptides, so-called sORF-encoded peptides (sPEPs), whose functions remain mainly unknown.In this study, we propose a system approach to determine the functions of sPEPs in monocytes. We first predicted the interactions of sPEPs with canonical proteins and analyzed the interfaces of interactions as well as the set of canonical proteins interacting with sPEPs. Second, by joining these sPEP-canonical protein interactions with the human interactome, we predicted the first sPEP interactome network to date. Based on its topology, we then predicted the function of the sPEPs. Our results suggest that the majority of sPEPs are involved in key biological functions, including regulatory functions, metabolism, and signaling. Overall, the diversity in the predicted functions of the sPEPs underlines the prevalence of their role in different biological mechanisms, suggesting that they are major regulatory actors.Competing Interest StatementThe authors have declared no competing interest.