PUBLICATION
            Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish
- Authors
- Chew, G.L., Pauli, A., Schier, A.F.
- ID
- ZDB-PUB-160525-9
- Date
- 2016
- Source
- Nature communications 7: 11663 (Journal)
- Registered Authors
- Pauli, Andrea, Schier, Alexander
- Keywords
- Biological sciences, Bioinformatics, Evolution, Genetics
- MeSH Terms
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                - Zebrafish
- Linear Models
- Amino Acid Sequence/genetics
- Protein Biosynthesis/genetics*
- Open Reading Frames/genetics*
- Models, Biological
- Sequence Analysis, RNA
- 5' Untranslated Regions/genetics
- Humans
- Conserved Sequence/genetics*
- Regulatory Sequences, Ribonucleic Acid/genetics*
- Ribosomes/genetics
- Ribosomes/metabolism
- Animals
- Molecular Sequence Annotation
- Mice
- RNA, Messenger/genetics*
 
- PubMed
- 27216465 Full text @ Nat. Commun.
            Citation
        
        
            Chew, G.L., Pauli, A., Schier, A.F. (2016) Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish. Nature communications. 7:11663.
        
    
                
                    
                        Abstract
                    
                    
                
                
            
        
        
    
        
            
            
 
    
    
        
    
    
    
        
                Upstream open reading frames (uORFs) are ubiquitous repressive genetic elements in vertebrate mRNAs. While much is known about the regulation of individual genes by their uORFs, the range of uORF-mediated translational repression in vertebrate genomes is largely unexplored. Moreover, it is unclear whether the repressive effects of uORFs are conserved across species. To address these questions, we analyse transcript sequences and ribosome profiling data from human, mouse and zebrafish. We find that uORFs are depleted near coding sequences (CDSes) and have initiation contexts that diminish their translation. Linear modelling reveals that sequence features at both uORFs and CDSes modulate the translation of CDSes. Moreover, the ratio of translation over 5' leaders and CDSes is conserved between human and mouse, and correlates with the number of uORFs. These observations suggest that the prevalence of vertebrate uORFs may be explained by their conserved role in repressing CDS translation.
            
    
        
        
    
    
    
                
                    
                        Genes / Markers
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Expression
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Phenotype
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Mutations / Transgenics
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Human Disease / Model
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Sequence Targeting Reagents
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Fish
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Orthology
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Engineered Foreign Genes
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Mapping
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    