Small nucleolar RNA landscapes uncover ribosome-modification potential and immune-metabolic signatures in bovine subclinical mastitis.

Subclinical mastitis (SCM) is a clinically silent inflammatory disorder that impairs udder health and milk productivity, yet how small nucleolar RNAs (snoRNAs) participate in epigenome-linked mammary remodeling remains poorly defined. We profiled snoRNAs in milk somatic cells from healthy and SCM-affected Vrindavani cows and integrated differentially expressed (DE) snoRNAs with matched methylome-transcriptome-derived differentially methylated expression genes (DMEGs). A catalogue of 2186 snoRNA loci was generated, and RNA-seq analysis identified 25 DE snoRNAs (FDR < 0.05, |log2FC= > 1), all showing increased abundance in SCM, including 19 C/D-box and 6 H/ACA-box snoRNAs. Computational target prediction identified 18 candidate H/ACA-box snoRNA-rRNA interactions consistent with pseudouridylation guidance and 47 candidate C/D-box interactions consistent with 2'-O-methylation guidance, predominantly involving 28S rRNA. Correlation-based integration of DE snoRNAs with DMEGs identified co-expression patterns associated with immune and metabolic processes. Positively correlated genes were enriched for leukocyte migration, granulocyte chemotaxis, cytokine/chemokine activity, immune receptor activity and MHC-associated host-defense pathways, whereas negatively correlated genes were enriched for oxoacid metabolism, glycolysis/gluconeogenesis, AMPK signaling, glycerolipid metabolism and peroxisome pathways. Together, these findings characterize SCM-associated snoRNA expression changes, predicted rRNA guide-target interactions and cross-layer associations with methylation-associated transcriptional programs, providing a hypothesis-generating framework for prioritizing snoRNAs for further experimental investigation.