Exploring the minor spliceosome snRNA as a Breakthrough Point for Basic Research Integrating Chinese and Western Medicine

Abstract:
[Abstract]Background Numerous unexplained experimental anomalies regarding the expression of minor spliceosome snRNAs and U12-type intron-containing genes have persisted for years, posing a long-standing challenge to the scientific community without a breakthrough.Objective To systematically review the literature on minor spliceosome snRNAs and propose/validate the hypothesis that in vivo, minor spliceosome snRNAs in neurons, cardiomyocytes, and other cells are not transcribed endogenously within the nucleus, but are instead secreted by renal tubular epithelial cells via exosomes and supplied to distant cells through systemic circulation. This study aims to provide a unified explanation for experimental anomalies in minor spliceosome snRNAs, the mechanisms underlying comorbidities of major diseases, aging, and the scientific essence of "Kidney Qi" in Traditional Chinese Medicine.Methods A systematic retrieval was conducted on 32 studies (1999–2026) concerning the localization, maternal compensation, kidney specificity, and aging of minor spliceosome snRNAs in vivoand in vitro, establishing an evidence chain for these "anomalous findings." In pilot experiments, HK-2 human renal tubular epithelial cells were used as a model; exosomes were isolated via ultracentrifugation, and the abundance of U11, U12, U4atac, and U6atac snRNAs was quantified using qPCR with dual internal controls. Results Literature integration suggests that cellular minor spliceosome snRNAs in vivolikely originate from exosomes secreted by renal tubular epithelial cells rather than from endogenous nuclear transcription. Pilot experiments confirmed the detection of U11, U12, and U4atac within HK-2-derived exosomes, with U12 showing the highest relative abundance. U6atac was nearly undetectable, presumably due to its extremely short half-life.  Limitations This study has not yet completed in vivotracing experiments to demonstrate the uptake of kidney-derived exosomal snRNAs by target organs. Furthermore, validation using renal tubule-specific snRNA knockout animal models to observe distal tissue phenotypes and functional splicing reconstitution assays remains to be performed.  Conclusion Integrating global unexpected findings on minor spliceosome snRNAs, the broad-spectrum antiviral logic of evolutionary biology, and preliminary experimental evidence, we propose that the "Renal Tubular Epithelial Cell Exosome–Minor Spliceosome snRNA" axis may represent a key trans-cellular supply pathway essential for maintaining the homeostasis of U12-type intron-containing genes throughout the body.