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Module Assembly Strategy for Single-Cell Nucleic Acid Imaging at the Sub-Molecule Level.

Xucong Teng1, Yicong Dai1, Jinghong Li1

  • 1Department of Chemistry, Center for BioAnalytical Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, 100084, Beijing, P. R. China.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|March 10, 2022
PubMed
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New single-cell imaging methods offer unprecedented sub-molecule insights into nucleic acids, visualizing RNA splicing, G-quadruplexes, mitochondrial DNA variations, and RNA methylation. This advancement enhances molecular recognition for deeper biological understanding.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biotechnology

Background:

  • Single-cell imaging preserves in situ cellular context, crucial for understanding intracellular nucleic acid behavior.
  • Traditional nucleic acid analysis often lacks the resolution to reveal sub-molecule details like secondary structures or individual nucleotide variations.

Purpose of the Study:

  • To review recent advancements in single-cell imaging techniques for sub-molecule level nucleic acid analysis.
  • To highlight key strategies and applications for visualizing complex nucleic acid structures and modifications within individual cells.

Main Methods:

  • Development of high-specificity and high-sensitivity imaging probes for nucleic acids.
  • Application of "Module Assembly" strategy for enhanced molecular recognition.
Keywords:
imaging agentsmolecular recognitionnucleic acidssingle-cell imagingsub-molecule level

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  • Visualization of RNA splicing variants, RNA G-quadruplexes, mitochondrial DNA single nucleotide variations, and RNA m6A methylation.
  • Main Results:

    • Demonstrated feasibility of visualizing nucleic acids at segment, subunit, secondary structure, and monomer levels in single cells.
    • Successfully applied "Module Assembly" for high-performance molecular recognition in complex cellular environments.
    • Provided examples of visualizing diverse nucleic acid features, including RNA modifications and genetic variations.

    Conclusions:

    • Single-cell imaging at the sub-molecule level is a powerful approach for detailed nucleic acid analysis.
    • "Module Assembly" is a key strategy for improving molecular recognition in this field.
    • Future research should focus on further enhancing sensitivity and specificity for even finer molecular insights.