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Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila
Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open-reading frames (smORFs). Here, we describe two peptides in Drosophi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9681215/ https://www.ncbi.nlm.nih.gov/pubmed/36346220 http://dx.doi.org/10.7554/eLife.82709 |
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author | Bosch, Justin A Ugur, Berrak Pichardo-Casas, Israel Rabasco, Jordan Escobedo, Felipe Zuo, Zhongyuan Brown, Ben Celniker, Susan Sinclair, David A Bellen, Hugo J Perrimon, Norbert |
author_facet | Bosch, Justin A Ugur, Berrak Pichardo-Casas, Israel Rabasco, Jordan Escobedo, Felipe Zuo, Zhongyuan Brown, Ben Celniker, Susan Sinclair, David A Bellen, Hugo J Perrimon, Norbert |
author_sort | Bosch, Justin A |
collection | PubMed |
description | Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open-reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of genes. |
format | Online Article Text |
id | pubmed-9681215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-96812152022-11-23 Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila Bosch, Justin A Ugur, Berrak Pichardo-Casas, Israel Rabasco, Jordan Escobedo, Felipe Zuo, Zhongyuan Brown, Ben Celniker, Susan Sinclair, David A Bellen, Hugo J Perrimon, Norbert eLife Genetics and Genomics Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open-reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of genes. eLife Sciences Publications, Ltd 2022-11-08 /pmc/articles/PMC9681215/ /pubmed/36346220 http://dx.doi.org/10.7554/eLife.82709 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Genetics and Genomics Bosch, Justin A Ugur, Berrak Pichardo-Casas, Israel Rabasco, Jordan Escobedo, Felipe Zuo, Zhongyuan Brown, Ben Celniker, Susan Sinclair, David A Bellen, Hugo J Perrimon, Norbert Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila |
title | Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila |
title_full | Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila |
title_fullStr | Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila |
title_full_unstemmed | Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila |
title_short | Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila |
title_sort | two neuronal peptides encoded from a single transcript regulate mitochondrial complex iii in drosophila |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9681215/ https://www.ncbi.nlm.nih.gov/pubmed/36346220 http://dx.doi.org/10.7554/eLife.82709 |
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