ArticleMolecular systems biology2011
Cell-to-cell variability of alternative RNA splicing.
Article in Molecular systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Coordinated alternative splicing decisions via stepwise exon definition.Nucleic acids research · 2026Article
- Novel LARS2 variants in patients with Perrault syndrome: expanding the genetic spectrum and phenotypic heterogeneity.Frontiers in genetics · 2026Article
- Omics-based dissection of alternative splicing and the regulatory architecture in fungal genomes.Current research in microbial sciences · 2026Review
- Single-Molecule Fluorescence In Situ Hybridization (smFISH) for RNA Localization Relative to a DNA Locus in Bacteria.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Position-dependent effects of RNA-binding proteins in the context of co-transcriptional splicing.NPJ systems biology and applications · 2023Article
- HiFENS: high-throughput FISH detection of endogenous pre-mRNA splicing isoforms.Nucleic acids research · 2022Article
- Single-Cell FISH Analysis Reveals Distinct Shifts in PKM Isoform Populations during Drug Resistance Acquisition.Biomolecules · 2022Article
- Illuminating RNA biology through imaging.Nature cell biology · 2022Review
- In Situ Imaging of mRNA Splicing Variants by SpliceRCA.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Imaging Organization of RNA Processing within the Nucleus.Cold Spring Harbor perspectives in biology · 2021Review
- Revised Exon Structure of l-DOPA Decarboxylase (International journal of molecular sciences · 2020Article
- Article
- Article
- Exon Definition Facilitates Reliable Control of Alternative Splicing in the RON Proto-Oncogene.Biophysical journal · 2020Article
- Obstacles to detecting isoforms using full-length scRNA-seq data.Genome biology · 2020Article
- Technological advances and computational approaches for alternative splicing analysis in single cells.Computational and structural biotechnology journal · 2020Review
- Imaging the Life and Death of mRNAs in Single Cells.Cold Spring Harbor perspectives in biology · 2018Review
- Splicing heterogeneity: separating signal from noise.Genome biology · 2018Article
- SpliceRCA:ACS central science · 2018Article
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Abstract
Heterogeneity in the expression levels of mammalian genes is large even in clonal populations and has phenotypic consequences. Alternative splicing is a fundamental aspect of gene expression, yet its contribution to heterogeneity is unknown. Here, we use single-molecule imaging to characterize the cell-to-cell variability in mRNA isoform ratios for two endogenous genes, CAPRIN1 and MKNK2. We show that isoform variability in non-transformed, diploid cells is remarkably close to the minimum possible given the stochastic nature of individual splicing events, while variability in HeLa cells is considerably higher. Analysis of the potential sources of isoform ratio heterogeneity indicates that a difference in the control over splicing factor activity is one origin of this increase. Our imaging approach also visualizes non-alternatively spliced mRNA and active transcription sites, and yields spatial information regarding the relationship between splicing and transcription. Together, our work demonstrates that mammalian cells minimize fluctuations in mRNA isoform ratios by tightly regulating the splicing machinery.
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