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Updated: Sep 26, 2025

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
Open reading frame dominance indicates protein-coding potential of RNAs
Yusuke Suenaga1, Mamoru Kato2, Momoko Nagai2
1Department of Molecular Carcinogenesis, Chiba Cancer Centre Research Institute, Chiba, Japan.
Researchers developed an ORF dominance score to understand RNA bifunctionality. This score reveals how sequence characteristics influence whether RNAs code for proteins or not, with implications for evolution in eukaryotes.
Area of Science:
- Molecular Biology
- Genomics
- Evolutionary Biology
Background:
- Many RNAs possess dual coding and noncoding functions.
- Sequence features dictating RNA bifunctionality are largely unknown.
- Understanding these features is crucial for RNA biology.
Purpose of the Study:
- To develop and validate a metric for RNA bifunctionality.
- To investigate sequence characteristics influencing coding and noncoding RNA roles.
- To explore evolutionary pressures shaping RNA bifunctionality.
Main Methods:
- Development of the open reading frame (ORF) dominance score.
- Calculation of ORF dominance as the ratio of the longest ORF to total putative ORF lengths.
- Analysis of ORF dominance across bacteria, archaea, and eukaryotes, including tissue-specific and ubiquitous transcripts.
Main Results:
- The ORF dominance score correlates with translation efficiency in coding RNAs and translation in noncoding RNAs.
- Eukaryotic coding and noncoding transcripts show broader ORF dominance distributions with significant overlap.
- Overlap extent correlates with genome mutation rates and inversely with effective population size; tissue-specific RNAs, particularly in testes, exhibit higher ORF dominance.
Conclusions:
- The ORF dominance score quantifies sequence-based RNA bifunctionality.
- Eukaryotic evolution, marked by decreased population size and testes development, facilitated the emergence of bifunctional RNAs.
- This study provides insights into the evolution of complex RNA functions in eukaryotes.
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