Limits...
Predicting translation initiation rates for designing synthetic biology.

Reeve B, Hargest T, Gilbert C, Ellis T - Front Bioeng Biotechnol (2014)

Bottom Line: Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5'-untranslated region and the start of the coding sequence.Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels.In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

View Article: PubMed Central - PubMed

Affiliation: Centre for Synthetic Biology and Innovation, Imperial College London , London , UK ; Department of Bioengineering, Imperial College London , London , UK.

ABSTRACT
In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5'-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

No MeSH data available.


An illustration of the translational initiation elements encoded in the 5′ untranslated region (5′-UTR) of an mRNA (A), and the three major events that affect prokaryotic translation initiation (B), following the model described by Na and Lee (2010). All three calculators estimate translation initiation by considering the difference in free energies between the initial state (unbound mRNA folded into secondary structures) and final (mRNA bound to a ribosome) state.
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Figure 1: An illustration of the translational initiation elements encoded in the 5′ untranslated region (5′-UTR) of an mRNA (A), and the three major events that affect prokaryotic translation initiation (B), following the model described by Na and Lee (2010). All three calculators estimate translation initiation by considering the difference in free energies between the initial state (unbound mRNA folded into secondary structures) and final (mRNA bound to a ribosome) state.

Mentions: The factors that influence the rate of translation initiation can be grouped into three categories (Figure 1). Firstly, the global folding and unfolding of transcribed mRNAs, whose secondary structures can hinder the binding of the ribosome: during translation initiation the transcribed mRNA folds in and out of the secondary structures, which may interfere with ribosome binding (de Smit and van Duin, 1990). Secondly, the regional folding and unfolding of nucleotides in the RBS region: the ribosome docking site (RDS), a sequence roughly 30 nucleotides around the start codon, must be unfolded and exposed for the ribosome recognition sequence to bind. Lastly, there is the efficiency of ribosome binding itself, which is determined by the binding affinities between the SD sequence and the complementary 16S rRNA anti-SD sequence (Na et al., 2010).


Predicting translation initiation rates for designing synthetic biology.

Reeve B, Hargest T, Gilbert C, Ellis T - Front Bioeng Biotechnol (2014)

An illustration of the translational initiation elements encoded in the 5′ untranslated region (5′-UTR) of an mRNA (A), and the three major events that affect prokaryotic translation initiation (B), following the model described by Na and Lee (2010). All three calculators estimate translation initiation by considering the difference in free energies between the initial state (unbound mRNA folded into secondary structures) and final (mRNA bound to a ribosome) state.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126478&req=5

Figure 1: An illustration of the translational initiation elements encoded in the 5′ untranslated region (5′-UTR) of an mRNA (A), and the three major events that affect prokaryotic translation initiation (B), following the model described by Na and Lee (2010). All three calculators estimate translation initiation by considering the difference in free energies between the initial state (unbound mRNA folded into secondary structures) and final (mRNA bound to a ribosome) state.
Mentions: The factors that influence the rate of translation initiation can be grouped into three categories (Figure 1). Firstly, the global folding and unfolding of transcribed mRNAs, whose secondary structures can hinder the binding of the ribosome: during translation initiation the transcribed mRNA folds in and out of the secondary structures, which may interfere with ribosome binding (de Smit and van Duin, 1990). Secondly, the regional folding and unfolding of nucleotides in the RBS region: the ribosome docking site (RDS), a sequence roughly 30 nucleotides around the start codon, must be unfolded and exposed for the ribosome recognition sequence to bind. Lastly, there is the efficiency of ribosome binding itself, which is determined by the binding affinities between the SD sequence and the complementary 16S rRNA anti-SD sequence (Na et al., 2010).

Bottom Line: Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5'-untranslated region and the start of the coding sequence.Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels.In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

View Article: PubMed Central - PubMed

Affiliation: Centre for Synthetic Biology and Innovation, Imperial College London , London , UK ; Department of Bioengineering, Imperial College London , London , UK.

ABSTRACT
In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5'-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.

No MeSH data available.