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Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames

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...

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Autores principales: Sandmann, Clara-L., Schulz, Jana F., Ruiz-Orera, Jorge, Kirchner, Marieluise, Ziehm, Matthias, Adami, Eleonora, Marczenke, Maike, Christ, Annabel, Liebe, Nina, Greiner, Johannes, Schoenenberger, Aaron, Muecke, Michael B., Liang, Ning, Moritz, Robert L., Sun, Zhi, Deutsch, Eric W., Gotthardt, Michael, Mudge, Jonathan M., Prensner, John R., Willnow, Thomas E., Mertins, Philipp, van Heesch, Sebastiaan, Hubner, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032668/
https://www.ncbi.nlm.nih.gov/pubmed/36806354
http://dx.doi.org/10.1016/j.molcel.2023.01.023
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author Sandmann, Clara-L.
Schulz, Jana F.
Ruiz-Orera, Jorge
Kirchner, Marieluise
Ziehm, Matthias
Adami, Eleonora
Marczenke, Maike
Christ, Annabel
Liebe, Nina
Greiner, Johannes
Schoenenberger, Aaron
Muecke, Michael B.
Liang, Ning
Moritz, Robert L.
Sun, Zhi
Deutsch, Eric W.
Gotthardt, Michael
Mudge, Jonathan M.
Prensner, John R.
Willnow, Thomas E.
Mertins, Philipp
van Heesch, Sebastiaan
Hubner, Norbert
author_facet Sandmann, Clara-L.
Schulz, Jana F.
Ruiz-Orera, Jorge
Kirchner, Marieluise
Ziehm, Matthias
Adami, Eleonora
Marczenke, Maike
Christ, Annabel
Liebe, Nina
Greiner, Johannes
Schoenenberger, Aaron
Muecke, Michael B.
Liang, Ning
Moritz, Robert L.
Sun, Zhi
Deutsch, Eric W.
Gotthardt, Michael
Mudge, Jonathan M.
Prensner, John R.
Willnow, Thomas E.
Mertins, Philipp
van Heesch, Sebastiaan
Hubner, Norbert
author_sort Sandmann, Clara-L.
collection PubMed
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.
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spelling pubmed-100326682023-03-23 Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames Sandmann, Clara-L. Schulz, Jana F. Ruiz-Orera, Jorge Kirchner, Marieluise Ziehm, Matthias Adami, Eleonora Marczenke, Maike Christ, Annabel Liebe, Nina Greiner, Johannes Schoenenberger, Aaron Muecke, Michael B. Liang, Ning Moritz, Robert L. Sun, Zhi Deutsch, Eric W. Gotthardt, Michael Mudge, Jonathan M. Prensner, John R. Willnow, Thomas E. Mertins, Philipp van Heesch, Sebastiaan Hubner, Norbert Mol Cell Resource 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. Cell Press 2023-03-16 /pmc/articles/PMC10032668/ /pubmed/36806354 http://dx.doi.org/10.1016/j.molcel.2023.01.023 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Resource
Sandmann, Clara-L.
Schulz, Jana F.
Ruiz-Orera, Jorge
Kirchner, Marieluise
Ziehm, Matthias
Adami, Eleonora
Marczenke, Maike
Christ, Annabel
Liebe, Nina
Greiner, Johannes
Schoenenberger, Aaron
Muecke, Michael B.
Liang, Ning
Moritz, Robert L.
Sun, Zhi
Deutsch, Eric W.
Gotthardt, Michael
Mudge, Jonathan M.
Prensner, John R.
Willnow, Thomas E.
Mertins, Philipp
van Heesch, Sebastiaan
Hubner, Norbert
Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
title Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
title_full Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
title_fullStr Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
title_full_unstemmed Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
title_short Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
title_sort evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032668/
https://www.ncbi.nlm.nih.gov/pubmed/36806354
http://dx.doi.org/10.1016/j.molcel.2023.01.023
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