Quantitative imaging of single mRNA splice variants in living cells

Kyuwan Lee, Yi Cui, Luke P. Lee, Joseph Irudayaraj

Research output: Contribution to journalArticlepeer-review


Alternative messenger RNA (mRNA) splicing is a fundamental process of gene regulation, and errors in RNA splicing are known to be associated with a variety of different diseases. However, there is currently a lack of quantitative technologies for monitoring mRNA splice variants in cells. Here, we show that a combination of plasmonic dimer probes and hyperspectral imaging can be used to detect and quantify mRNA splice variants in living cells. The probes are made from gold nanoparticles functionalized with oligonucleotides and can hybridize to specific mRNA sequences, forming nanoparticle dimers that exhibit distinct spectral shifts due to plasmonic coupling. With this approach, we show that the spatial and temporal distribution of three selected splice variants of the breast cancer susceptibility gene, BRCA1, can be monitored at single-copy resolution by measuring the hybridization dynamics of the nanoplasmonic dimers. Our study provides insights into RNA and its transport in living cells, which could improve our understanding of cellular protein complexes, pharmacogenomics, genetic diagnosis and gene therapies.

Original languageEnglish (US)
Pages (from-to)474-480
Number of pages7
JournalNature Nanotechnology
Issue number6
StatePublished - Jun 2014
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • General Materials Science
  • Condensed Matter Physics
  • Electrical and Electronic Engineering


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