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

Abstract: [Abstract]Background For many years, numerous experimental anomalies related to the expression of minor spliceosome snRNAs and U12-type introns have remained unexplained, with their underlying mechanisms elusive and a lack of breakthroughs in the field.Objective This study systematically reviews experimental literature on minor spliceosome snRNAs and proposes and tests a hypothesis: in vivo, minor spliceosome snRNAs in neurons, cardiomyocytes, and other cells are not transcribed within their own nuclei but are instead secreted by renal tubular epithelial cells via exosomes and distributed via bodily fluid circulation to supply other cells. This framework aims to provide a unified explanation for experimental anomalies in minor spliceosome snRNA research, mechanisms of comorbidity in major diseases, aging, and the scientific basis of "kidney qi" in traditional Chinese medicine.Methods A total of 32 studies (1999–2025) on the localization, maternal compensation, kidney specificity, and aging-related aspects of minor spliceosome snRNAs in vivo/in vitro were reviewed to construct an "anomaly evidence chain." A preliminary experiment was conducted using HK-2 human renal tubular epithelial cells as a model: exosomes were isolated via ultracentrifugation, and the abundance of U11, U12, U4atac, and U6atac snRNAs was quantified by qPCR with dual internal controls.Results Literature integration suggests that minor spliceosome snRNAs in cells in vivo may originate from renal tubular epithelial cell exosomes rather than from de novo nuclear transcription. Preliminary experiments: U11, U12, and U4atac were detected in HK-2 exosomes, with U12 showing the highest relative abundance; U6atac was nearly undetectable likely due to its extremely short half-life.Limitations The following steps have not yet been completed: in vivo tracing experiments to demonstrate uptake of kidney-derived minor spliceosome snRNA exosomes by target organs; validation of distal tissue phenotypes using renal tubular-specific snRNA knockout animal models; and functional splicing reconstitution experiments using exosomal minor spliceosome snRNAs.Conclusion Synthesizing global unexpected findings and preliminary experimental evidence on minor spliceosome snRNAs, this study suggests that the "renal tubular epithelial cell exosome–minor spliceosome snRNA" axis may be a key transcellular supply pathway for maintaining systemic homeostasis of U12-type intron-containing genes.