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Cultural frameworks for understanding the self are often categorized into two broad orientations: individualism and collectivism. These paradigms influence how people define themselves, relate to others, and interpret their social worlds. Each orientation offers distinct perspectives on autonomy, responsibility, and the role of the individual within a community.Individualistic CulturesIn individualistic cultures like North America and Western Europe, identity is understood as autonomous and...
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Olfactory Context Dependent Memory: Direct Presentation of Odorants
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Rationalizing Context-Dependent Performance of Dynamic RNA Regulatory Devices.

Ross Kent1, Samantha Halliwell1, Kate Young1

  • 1Manchester Institute of Biotechnology, School of Chemistry , University of Manchester , Manchester , M13 9PL , United Kingdom.

ACS Synthetic Biology
|June 22, 2018
PubMed
Summary

Altering synonymous codon usage in RNA sequences can engineer novel RNA regulatory devices. This study presents a framework to understand and optimize RNA device performance for synthetic biology applications.

Keywords:
RNA device integrationRNA foldingcodon usagegene expression controlriboswitch

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Area of Science:

  • Synthetic Biology
  • Molecular Biology
  • Biochemistry

Background:

  • RNA's information processing capabilities are valuable for synthetic biology.
  • RNA function is context-dependent, limiting modularity of RNA regulatory devices.
  • Translational ON riboswitches are sensitive to sequence context in their 5' untranslated region (UTR).

Purpose of the Study:

  • To investigate the cause and effect of sequence context sensitivity in translational ON riboswitches.
  • To engineer RNA devices with varied functional properties by altering N-terminal codon usage.
  • To develop a multivariant analysis framework for rational riboswitch engineering.

Main Methods:

  • Construction and screening of a library of N-terminal synonymous codon variants.
  • Application of linear regression to identify key features for optimal riboswitch performance.
  • Utilizing partial least squares (PLS) analysis to model metric effects on performance.

Main Results:

  • Synonymous codon variants yielded RNA devices with diverse functional outputs (ON, OFF, fold-change).
  • Identified key determining features and interactions influencing riboswitch performance.
  • Developed a PLS model that effectively explains the observed library performance.

Conclusions:

  • Synonymous codon context significantly impacts allosteric RNA device performance.
  • The developed multivariant analysis framework aids in rational riboswitch engineering.
  • This framework provides a platform for future context-aware engineering of RNA devices.