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Related Concept Videos

RNA Editing02:23

RNA Editing

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Translational Regulation01:29

Translational Regulation

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Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
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Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Improving Translational Accuracy02:07

Improving Translational Accuracy

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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Updated: Aug 7, 2025

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
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Autocatalytic base editing for RNA-responsive translational control.

Raphaël V Gayet1,2,3,4, Katherine Ilia1,2, Shiva Razavi1,2,4,5

  • 1Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.

Nature Communications
|March 11, 2023
PubMed
Summary

Researchers developed a smart RNA sensor system called DART VADAR that amplifies genetic signals. This programmable tool detects specific RNA sequences and controls gene translation for potential therapeutic applications.

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RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
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Area of Science:

  • Synthetic Biology
  • Molecular Biology
  • Genetic Engineering

Background:

  • Smart therapeutics require genetic circuits for controlled transgene expression.
  • Existing systems lack efficient signal amplification and programmability.

Purpose of the Study:

  • To engineer programmable single-transcript RNA sensors for detecting transcriptional cues.
  • To develop a system with high dynamic range and minimal off-target effects.

Main Methods:

  • Engineered adenosine deaminases acting on RNA (ADARs) to create a positive feedback loop for signal amplification.
  • Developed DART VADAR (Detection and Amplification of RNA Triggers via ADAR) system.
  • Utilized a hyperactive ADAR variant and orthogonal RNA targeting.

Main Results:

  • Achieved signal amplification through autocatalytic editing and a positive feedback loop.
  • Demonstrated high dynamic range, low background, and minimal off-target effects.
  • Successfully detected single nucleotide polymorphisms and modulated translation in mammalian cells.

Conclusions:

  • DART VADAR offers a powerful platform for programmable gene expression control.
  • The system's efficiency and specificity enable potential applications in diagnostics and therapeutics.
  • This technology advances the development of responsive genetic circuits.