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Elife. 2017 Oct 30;6. pii: e27860. doi: 10.7554/eLife.27860.

Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins.

Author information

1
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada.
2
PROTEO, Québec Network for Research on Protein Function, Structure and Engineering, Québec, Canada.
3
INSERM U1192, Laboratoire Protéomique, Réponse Inflammatoire & Spectrométrie de Masse (PRISM) F-59000 Lille, Université de Lille, Lille, France.
4
Department of Biology, Université de Sherbrooke, Québec, Canada.
5
Center for Scientific computing, Information Technologies Services,, Université de Sherbrooke, Québec, Canada.
6
Département de biochimie, microbiologie et bioinformatique, Université Laval, Québec, Canada.
7
IBIS, Université Laval, Québec, Canada.
8
Department of Computer Science, Université de Sherbrooke, Québec, Canada.
9
Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Québec, Canada.
10
Department of Family Medicine, Université de Sherbrooke, Québec, Canada.
#
Contributed equally

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.

KEYWORDS:

alternative translation; biochemistry; computational biology; human; open reading frames; small proteins; systems biology; translation; translation initiation sites

PMID:
29083303
PMCID:
PMC5703645
DOI:
10.7554/eLife.27860
[Indexed for MEDLINE]
Free PMC Article

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