Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins
Abstract
Recent functional, proteomic and ribosome profiling studies in eukaryotes have concurrently demonstrated the translation of alternative open reading frames (altORFs) in addition to annotated protein coding sequences (CDSs). We show that a large number of small proteins could in fact be coded by these altORFs. The putative alternative proteins translated from altORFs have orthologs in many species and contain functional domains. Evolutionary analyses indicate that altORFs often show more extreme conservation patterns than their CDSs. Thousands of alternative proteins are detected in proteomic datasets by reanalysis using a database containing predicted alternative proteins. This is illustrated with specific examples, including altMiD51, a 70 amino acid mitochondrial fission-promoting protein encoded in MiD51/Mief1/SMCR7L, a gene encoding an annotated protein promoting mitochondrial fission. Our results suggest that many genes are multicoding genes and code for a large protein and one or several small proteins.
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Funding
Canadian Institutes of Health Research (MOP-137056)
- Xavier Roucou
Canada Research Chairs
- Aïda Ouangraoua
- Christian R Landry
- Xavier Roucou
Fonds de Recherche du Québec - Nature et Technologies (2015-PR-181807)
- Christian R Landry
- Xavier Roucou
Merck Sharp and Dohme
- Xavier Roucou
Canadian Institutes of Health Research (MOP-136962)
- Xavier Roucou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nir Ben-Tal, Tel Aviv University, Israel
Version history
- Received: April 17, 2017
- Accepted: October 29, 2017
- Accepted Manuscript published: October 30, 2017 (version 1)
- Version of Record published: November 27, 2017 (version 2)
Copyright
© 2017, Samandi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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