Selective remodeling of snoRNA and sdRNA biology in glioblastoma

Small nucleolar RNAs (snoRNAs) are best known as guide RNAs for ribosomal RNA modification, but accumulating evidence indicates that their biology extends beyond canonical ribosome maturation. Across GBM-specific and broader glioma studies, snoRNAs, snoRNA-derived RNAs (sdRNAs), and associated small nucleolar ribonucleoprotein components are emerging as regulators of malignant cell states. This review frames GBM-associated snoRNA and sdRNA alterations as a cell-biological remodeling process that links ribosome biogenesis, metabolic adaptation, treatment response, and extracellular-vesicle output. Across currently available GBM and broader glioma studies, tumor-restraining C/D-box snoRNAs, including SNORD76, SNORD47, SNORD44, and SNORD113-3, tend to be reduced, and restoration of several of these molecules suppresses malignant phenotypes in their respective experimental systems. Conversely, tumor-supporting snoRNA-associated activities, including the U3-PHAX-DNA-PKcs-TRIM24 complex, a U3-derived small RNA acting through ZBTB7A, and preprint-based H/ACA snoRNA/snoRNP activity involving dyskerin, are maintained, increased, or functionally co-opted in specific GBM-related contexts. These alterations converge on three recurrent cellular contexts: translational capacity, glucose and glycolipid metabolism, and survival under radiotherapy or temozolomide. Treatment-associated senescence may also reshape extracellular-vesicle snoRNA cargo, with SNORA49 detected in a small longitudinal plasma series, although this remains exploratory rather than a validated liquid-biopsy marker. We also emphasize the need to distinguish snoRNAs and sdRNAs from their SNHG host transcripts, because these molecular entities have distinct biogenesis and mechanisms. Together, these studies suggest a context-dependent pattern of snoRNA and sdRNA dysregulation across GBM and related glioma models, with the strength of evidence varying among individual molecular axes. SnoRNAs and sdRNAs should be viewed as an emerging regulatory layer in GBM rather than as established therapeutic targets. Future work should validate molecule-specific snoRNA and sdRNA axes in disease-relevant models and determine whether extracellular-vesicle snoRNAs provide reproducible readouts of treatment-associated cell states.