ArticleGenes & development2015
Synonymous modification results in high-fidelity gene expression of repetitive protein and nucleotide sequences.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 108 citations in OpenAlex.
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- Establishing MS2-MCP-based single-molecule RNA visualization in Schizosaccharomyces pombe.Journal of cell science · 2026Article
- Enhancement of RNA Imaging Platforms by the Use of Peptide Nucleic Acid-Based Linkers.Bio-protocol · 2026Article
- Robust mammalian RNA localization elements are complex and multipartite.bioRxiv : the preprint server for biology · 2026Article
- A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation.Nature communications · 2026Article
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- Establishing MS2-MCP-based single-molecule RNA visualization inbioRxiv : the preprint server for biology · 2026Article
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- A new single chain, genetically encoded biosensor for RhoB GTPase based on FRET, useful for live-cell imaging.bioRxiv : the preprint server for biology · 2026Article
- Orthogonal RNA-regulated destabilization domains for three-color RNA imaging with minimal RNA perturbation.Nature methods · 2026Article
- Single-protein/RNA imaging reveals ZNF598 as a limiting factor in resolving collided ribosomes.The EMBO journal · 2025Article
- Structural basis for ring-opening fluorescence by the RhoBAST RNA aptamer.Nucleic acids research · 2025Article
- Unravelling molecular dynamics in living cells: Fluorescent protein biosensors for cell biology.Journal of microscopy · 2025Review
- G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration.Cell reports · 2025Article
- Synthetic anti-RNA antibody derivatives for RNA visualization in mammalian cells.Nucleic acids research · 2025Article
- MONITTR allows real-time imaging of transcription and endogenous proteins in C. elegans.The Journal of cell biology · 2025Article
- DNA break induces rapid transcription repression mediated by proteasome-dependent RNAPII removal.Cell reports · 2024Article
- Translation Dynamics of Single mRNAs in Live Cells.Annual review of biophysics · 2024Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Repetitive nucleotide or amino acid sequences are often engineered into probes and biosensors to achieve functional readouts and robust signal amplification. However, these repeated sequences are notoriously prone to aberrant deletion and degradation, impacting the ability to correctly detect and interpret biological functions. Here, we introduce a facile and generalizable approach to solve this often unappreciated problem by modifying the nucleotide sequences of the target mRNA to make them nonrepetitive but still functional ("synonymous"). We first demonstrated the procedure by designing a cassette of synonymous MS2 RNA motifs and tandem coat proteins for RNA imaging and showed a dramatic improvement in signal and reproducibility in single-RNA detection in live cells. The same approach was extended to enhancing the stability of engineered fluorescent biosensors containing a fluorescent resonance energy transfer (FRET) pair of fluorescent proteins on which a great majority of systems thus far in the field are based. Using the synonymous modification to FRET biosensors, we achieved correct expression of full-length sensors, eliminating the aberrant truncation products that often were assumed to be due to nonspecific proteolytic cleavages. Importantly, the biological interpretations of the sensor are significantly different when a correct, full-length biosensor is expressed. Thus, we show here a useful and generally applicable method to maintain the integrity of expressed genes, critical for the correct interpretation of probe readouts.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.