| Title: |
Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames |
| Authors: |
Sandmann, C.L.; Schulz, J.F.; Ruiz-Orera, J.; Kirchner, M.; Ziehm, M.; Adami, E.; Marczenke, M.; Christ, A.; Liebe, N.; Greiner, J.; Schoenenberger, A.; Mücke, M.B.; Liang, N.; Moritz, R.L.; Sun, Z.; Deutsch, E.W.; Gotthardt, M.; Mudge, J.M.; Prensner, J.R.; Willnow, T.E.; Mertins, P.; van Heesch, S.; Hubner, N. |
| Publisher Information: |
Cell Press |
| Publication Year: |
2023 |
| Collection: |
Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| Subject Terms: |
Cardiovascular and Metabolic Diseases; Technology Platforms; Topic 1: Genes; Cells and Cell-Based Medicine; Topic 2: Molecular Processes and Therapies; Topic 3: Integrative Biomedicine |
| Description: |
All species continuously evolve short open reading frames (sORFs) that can be templated for protein synthesis and may provide raw materials for evolutionary adaptation. We analyzed the evolutionary origins of 7,264 recently cataloged human sORFs and found that most were evolutionarily young and had emerged de novo. We additionally identified 221 previously missed sORFs potentially translated into peptides of up to 15 amino acids-all of which are smaller than the smallest human microprotein annotated to date. To investigate the bioactivity of sORF-encoded small peptides and young microproteins, we subjected 266 candidates to a mass-spectrometry-based interactome screen with motif resolution. Based on these interactomes and additional cellular assays, we can associate several candidates with mRNA splicing, translational regulation, and endocytosis. Our work provides insights into the evolutionary origins and interaction potential of young and small proteins, thereby helping to elucidate this underexplored territory of the human proteome. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; other |
| Language: |
English |
| Relation: |
https://edoc.mdc-berlin.de/id/eprint/23156/1/23156oa.pdf; https://edoc.mdc-berlin.de/id/eprint/23156/7/23156suppl.zip; Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames. Sandmann, C.L., Schulz, J.F., Ruiz-Orera, J., Kirchner, M., Ziehm, M., Adami, E., Marczenke, M., Christ, A., Liebe, N., Greiner, J., Schoenenberger, A., Mücke, M.B., Liang, N., Moritz, R.L., Sun, Z., Deutsch, E.W., Gotthardt, M., Mudge, J.M., Prensner, J.R., Willnow, T.E., Mertins, P., van Heesch, S. and Hubner, N. Molecular Cell 83 (6): 994-1011.e18. 16 March 2023; PMID:36806354; https://doi.org/10.1016/j.molcel.2023.01.023 |
| DOI: |
10.1016/j.molcel.2023.01.023 |
| Availability: |
https://edoc.mdc-berlin.de/id/eprint/23156/; https://edoc.mdc-berlin.de/23156/; https://doi.org/10.1016/j.molcel.2023.01.023 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.998277AF |
| Database: |
BASE |