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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
A survey of mRNA sequences with a non-AUG start codon in RefSeq database
Suhas Tikole1, Ramasubbu Sankararamakrishnan
1Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur-208 016, India.
Journal of Biomolecular Structure & Dynamics
|June 20, 2006
Summary
Alternative translation initiation using non-AUG codons synthesizes multiple proteins from one mRNA. These alternative start codons are found in about 0.1% of mRNAs, often in regulatory and signaling proteins.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Alternative translation initiation allows synthesis of multiple proteins from a single messenger RNA (mRNA).
- Experimental studies have documented translation initiation at non-AUG codons, deviating from the canonical start site.
Purpose of the Study:
- To analyze the prevalence and characteristics of messenger RNA (mRNA) sequences initiating with non-AUG codons (nonAUG mRNAs).
- To investigate the functional implications and sequence context of alternative translation initiation.
- To establish a comprehensive database of nonAUG mRNAs.
Main Methods:
- Analysis of all mRNA sequences in the RefSeq database.
- Prediction of nonAUG mRNAs from genomic sequences.
- Curation and annotation of nonAUG sequences.
- Development of the "nonAUG" database.
Main Results:
- Approximately 0.1% of total mRNA sequences initiate translation with a non-AUG codon.
- A significant fraction of nonAUG mRNAs are predicted from genomic sequences.
- 52 curated nonAUG sequences explicitly use alternate start codons.
- Proteins translated from nonAUG codons are often involved in DNA/RNA binding, kinase activity, growth factors, immune response, or cell proliferation, suggesting regulatory or signaling roles.
- Conserved sequence motifs (purine at -3 and/or G at +4) are identified around non-AUG start codons.
- Genes with nonAUG initiation often produce alternate transcripts or multiple isoforms.
Conclusions:
- Alternative translation initiation at non-AUG codons is a significant biological mechanism.
- Proteins derived from nonAUG mRNAs play crucial roles in cellular regulation and signaling.
- The identified sequence contexts and conserved motifs provide insights into the regulation of alternative translation initiation.
- The "nonAUG" database serves as a valuable resource for researchers studying alternative translation initiation.
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