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09:37
An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
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Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins
Sondos Samandi1,2, Annie V Roy1,2, Vivian Delcourt1,2,3
1Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada.
Elife
|October 31, 2017
Summary
Many eukaryotic genes code for small proteins via alternative open-reading frames (altORFs), not just annotated sequences. These altORFs are conserved and detected in proteomic data, suggesting genes are often multicoding.
Area of Science:
- Genomics and Proteomics
- Molecular Biology
- Evolutionary Biology
Background:
- Recent studies reveal translation of alternative open-reading frames (altORFs) alongside annotated protein coding sequences (CDSs) in eukaryotes.
- These altORFs can encode small proteins, expanding the known proteome.
Purpose of the Study:
- To investigate the prevalence and functional significance of proteins encoded by altORFs.
- To demonstrate that many genes are multicoding, producing both large and small proteins.
Main Methods:
- Analysis of functional, proteomic, and ribosome profiling data.
- Reanalysis of proteomic datasets using a database of predicted alternative proteins.
- Evolutionary conservation analyses of altORFs and CDSs.
Main Results:
- A large number of small proteins are encoded by altORFs, with many possessing orthologs and functional domains across species.
- altORFs exhibit significant evolutionary conservation, sometimes exceeding that of their associated CDSs.
- Thousands of alternative proteins were identified in proteomic datasets, including the mitochondrial fission-promoting protein altMiD51.
Conclusions:
- Many eukaryotic genes are multicoding, capable of producing both annotated proteins and additional small proteins from altORFs.
- The discovery of altORF-encoded proteins significantly expands our understanding of the functional proteome and gene potential.
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