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An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences
Ivaylo P Ivanov1, Andrew E Firth, Audrey M Michel
1BioSciences Institute, University College Cork, Cork, Ireland. iivanov@genetics.utah.edu
Nucleic Acids Research
|January 27, 2011
Summary
This study reveals that non-AUG translation initiation is more common in humans than previously thought, expanding our understanding of gene expression and protein diversity. This finding improves the accuracy of gene annotations and highlights potential new regulatory mechanisms.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Eukaryotic translation initiation typically starts at the AUG start codon near the 5' cap of messenger RNA.
- Non-AUG initiation, using codons like CUG or UUG, has been observed but its full extent in humans is unclear.
- Accurate coding sequence annotation is crucial for understanding gene function and regulation.
Purpose of the Study:
- To investigate the prevalence and conservation of non-AUG translation initiation in human genes.
- To identify novel non-AUG-initiated N-terminal extensions and improve coding sequence annotations.
- To explore the potential for increased coding capacity and novel regulatory mechanisms through non-AUG initiation.
Main Methods:
- Developed a methodology using phylogenetic analysis of predicted 5' untranslated regions from orthologous genes.
- Utilized evolutionary signatures of protein-coding sequences to detect upstream translation initiation.
- Cross-referenced findings with published literature and ribosome profiling data for experimental validation.
Main Results:
- Identified 42 novel conserved potential non-AUG-initiated N-terminal extensions in human genes.
- Confirmed the conservation of known non-AUG-initiated extensions in 17 additional genes.
- Provided experimental evidence for non-AUG-initiated products in several cases.
Conclusions:
- Non-AUG translation initiation is a significant phenomenon in human gene expression, contributing to protein diversity.
- The findings enhance the quality of coding sequence annotations and reveal potential new regulatory pathways.
- This work underscores the importance of considering non-AUG initiation for a comprehensive understanding of the human genome.
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