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Engineering the 5' UTR-Mediated Regulation of Protein Abundance in Yeast Using Nucleotide Sequence Activity Relationships
- Source :
- ACS synthetic biology. 7(12)
- Publication Year :
- 2018
-
Abstract
- The 5′ untranslated region (5′UTR) plays a key role in post-transcriptional regulation, but interaction between nucleotides and directed evolution of 5′UTRs as synthetic regulatory elements remain unclear. By constructing a library of synthesized random 5′UTRs of 24 nucleotides in Saccharomyces cerevisiae, we observed strong epistatic interactions among bases from different positions in the 5′UTR. Taking into account these base interactions, we constructed a mathematical model to predict protein abundance with a precision of R2 = 0.60. On the basis of this model, we developed an approach to engineer 5′UTRs according to nucleotide sequence activity relationships (NuSAR), in which 5′UTRs were engineered stepwise through repeated cycles of backbone design, directed screening, and model reconstruction. After three rounds of NuSAR, the predictive accuracy of our model was improved to R2 = 0.71, and a strong 5′UTR was obtained with 5-fold higher protein abundance than the starting 5′UTR. Our findings provide ne...
- Subjects :
- 0301 basic medicine
Untranslated region
Five prime untranslated region
Saccharomyces cerevisiae
Green Fluorescent Proteins
Biomedical Engineering
Oligonucleotides
Computational biology
Regulatory Sequences, Nucleic Acid
Biochemistry, Genetics and Molecular Biology (miscellaneous)
03 medical and health sciences
Translational regulation
Nucleotide
chemistry.chemical_classification
biology
Base Sequence
Nucleic acid sequence
General Medicine
Models, Theoretical
biology.organism_classification
Directed evolution
030104 developmental biology
chemistry
Epistasis
Directed Molecular Evolution
5' Untranslated Regions
Genetic Engineering
Plasmids
Subjects
Details
- ISSN :
- 21615063
- Volume :
- 7
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- ACS synthetic biology
- Accession number :
- edsair.doi.dedup.....b9183d53b5d56ce0ddbfb9560af360ba