Engineering bacterial translation initiation — Do we have all the tools we need?
Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene ex...
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| Published in | Biochimica et biophysica acta. General subjects Vol. 1861; no. 11; pp. 3060 - 3069 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.11.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0304-4165 1872-8006 |
| DOI | 10.1016/j.bbagen.2017.03.008 |
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| Abstract | Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts.
Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals.
Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools.
Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O’Donoghue.
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•RNA-mediated regulation mechanisms control gene expression post-translationally.•Unraveling translation initiation mechanisms has enabled rational design tools.•Bioengineers have successfully exploited RNA-based regulation strategies.•Limitations exist regarding predictability, portability, and dynamic range.•Non-canonical mechanisms will provide tools to address engineering challenges. |
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| AbstractList | Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts.
Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals.
Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools.
Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O’Donoghue.
[Display omitted]
•RNA-mediated regulation mechanisms control gene expression post-translationally.•Unraveling translation initiation mechanisms has enabled rational design tools.•Bioengineers have successfully exploited RNA-based regulation strategies.•Limitations exist regarding predictability, portability, and dynamic range.•Non-canonical mechanisms will provide tools to address engineering challenges. Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts. Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals. Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools. Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts.Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals.Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools.Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O’Donoghue. Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts.BACKGROUNDReliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts.Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals.SCOPE OF REVIEWHere we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals.Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools.MAJOR CONCLUSIONSDue to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools.Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.GENERAL SIGNIFICANCEPredictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. |
| Author | Wieden, Hans-Joachim Vigar, Justin R.J. |
| Author_xml | – sequence: 1 givenname: Justin R.J. surname: Vigar fullname: Vigar, Justin R.J. – sequence: 2 givenname: Hans-Joachim surname: Wieden fullname: Wieden, Hans-Joachim email: hj.wieden@uleth.ca |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28315412$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1093_synbio_ysac017 crossref_primary_10_1016_j_procbio_2018_10_011 crossref_primary_10_1042_BCJ20210535 crossref_primary_10_1080_07388551_2024_2391881 crossref_primary_10_1021_acssynbio_2c00139 crossref_primary_10_1016_j_ymben_2018_04_008 crossref_primary_10_1016_j_biotechadv_2020_107512 crossref_primary_10_1038_s41467_020_17222_4 crossref_primary_10_1093_nar_gkac697 crossref_primary_10_1007_s12033_024_01248_w |
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| Keywords | Synthetic biology Rational design Ribosome engineering RNA engineering Translation initiation Riboregulation |
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| SubjectTerms | bacteria Bacteria - genetics Bacteria - metabolism Codon, Initiator - genetics Codon, Initiator - metabolism Escherichia coli gene expression Gene Expression Regulation, Bacterial ligands messenger RNA Peptide Chain Initiation, Translational - genetics Protein Biosynthesis - genetics Protein Engineering - methods protein synthesis Rational design regulatory sequences Riboregulation Ribosome engineering ribosomes Ribosomes - metabolism RNA engineering RNA, Messenger - genetics RNA, Messenger - metabolism RNA-binding proteins Synthetic biology synthetic genes translation (genetics) Translation initiation |
| Title | Engineering bacterial translation initiation — Do we have all the tools we need? |
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