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Researchers have introduced TotalX, a scalable method for single-cell total RNA sequencing. Traditionally, single-cell atlases focused only on polyadenylated (poly(A)) transcripts. Consequently, these maps missed crucial noncoding RNAs that regulate gene expression. This new framework integrates with standard droplet-based platforms. Therefore, it offers a unified pipeline for diverse RNA biotypes, including miRNA and tRNA.
The study applied TotalX to the developing human brain. The team identified biotype-specific programs across all neuronal lineages. Specifically, they tracked microRNA dynamics in Cajal-Retzius neurons. Furthermore, researchers found a significant anticorrelation between MIR137 and its targets. Since MIR137 is linked to schizophrenia and intellectual disability, this discovery suggests tight regulatory control during cortical development.
Beyond neurology, the framework analyzed human peripheral blood mononuclear cells (PBMCs). It identified transcriptional modules combining coding and noncoding RNAs. Additionally, the researchers studied dengue-infected hepatocytes. TotalX successfully captured non-adenylated viral transcripts. This capability allows doctors to distinguish infection states more accurately. Indeed, this expanded coverage helps in understanding cellular identity and gene regulation at the atlas scale.
Standard methods primarily capture polyadenylated messenger RNA. TotalX expands this by capturing noncoding RNAs, including microRNA and tRNA, using a unified droplet-based pipeline.
MIR137 is a microRNA associated with schizophrenia and intellectual disability. This sequencing technology reveals its specific enrichment in Cajal-Retzius neurons. It shows how noncoding RNA guides early brain development.
Disclaimer: This content is for informational and educational purposes only. It is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
Isakova A et al. Scalable single-cell total RNA sequencing unifies coding and noncoding transcriptomics. Nat Biotechnol. 2026 Mar 31. doi: 10.1038/s41587-026-03068-6. PMID: 41917462.
Duan J, et al. MIR137 and its target genes in schizophrenia. North Am J Med Sci. 2014.
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TotalX enables scalable single-cell total RNA sequencing, capturing coding and noncoding RNAs to reveal regulatory insights in brain development and infecti...
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