Small nucleolar RNAs (snoRNAs) are 60~300 nt, evolutionarily conserved small non-coding RNAs enriched in the nucleolus. snoRNAs can be classified into C/D box (SNORD) snoRNAs and H/ACA box (SNORA) snoRNAs that direct 2′-O-methylation and pseudouridylation of rRNAs, snRNAs and tRNAs, respectively. snoRNAs also aid pre-rRNA cleavage and, in some cases, mRNA splicing or 3′-end maturation. When packaged into extracellular vesicles, snoRNAs may mediate intercellular communication[1].

snoRNAs can be processed into snoRNA-derived small RNA fragments (sdRNAs) that may function similarly to miRNAs or piRNAs[1].

Recent studies have redefined snoRNAs as multifunctional regulators in addition to RNA modification: they act as protein-scaffolding platforms in gametogenesis [2], control ribosome assembly and p53-driven cell senescence via direct RPL23 interaction [3] (Fig. 1), direct secretory mRNAs to the signal recognition particle (SRP) machinery through ternary RNA gluing [4] (Fig. 2), reprogram chromatin by disrupting PRC2 to derepress ESM1 in fibroblast-like synoviocytes of Rheumatoid arthritis (RA) [5], and ameliorate differentiation defects in myotonic dystrophy[6]. Collectively, these findings establish snoRNAs as versatile trans-acting organizers of gene expression, protein trafficking, and cell fate that operate beyond their canonical rRNA-guided roles.

Figure 1. snoRNA drives p53-mediated cell senescence by blocking ribosomal protein uptake into nascent subunits[3].

Figure 2. snoRNA functions as a “molecular glue” that connects secretory protein mRNAs to the signal recognition particle (SRP) complex through novel ternary RNA interactions[4].

Dysregulated snoRNAs can act as oncogenes or tumor suppressors in cancers[7], mediate cancer treatment resistance[8] (Fig. 3), contribute to cardiovascular disorders such as hypertrophic/dilated cardiomyopathy and myocardial infarction (Fig. 4); play roles in neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s), Prader-Willi syndrome, and leukoencephalopathy [7, 9] (Fig. 5). Due to their stability in biofluids, tissue specificity, and disease correlation, snoRNAs hold strong potential as non-invasive biomarkers and therapeutic targets.

Figure 3. snoRNA contribute to cancer treatment resistance[8].

Figure 4. snoRNA contribute to cardiovascular diseases[9].

Figure 5. snoRNAs play roles in neurodegenerative diseases [7].

References
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