Small Nucleolar RNAs, Big Impact: Biogenesis, Mechanisms, and Roles in Health and Disease

Non-coding RNAs (ncRNAs) are a diverse class of regulatory molecules classified by their size, localization, and function. Among them, small nucleolar RNAs (snoRNAs) are 60-300-nucleotide small non-coding RNAs that are primarily encoded within intronic regions of protein-coding or non-coding host genes. They are broadly categorized into three types: C/D box snoRNAs (SNORDs), H/ACA box snoRNAs (SNORAs), and Cajal body-specific RNAs (scaRNAs). SNORDs and SNORAs primarily mediate RNA modifications through 2'-O-methylation (Nm) and pseudouridylation (Ψ), respectively, whereas scaRNAs specialize in modifying small nuclear RNAs (snRNAs) within the Cajal body, which is crucial for splicing processes. Recent discoveries have broadened the functional landscape of snoRNAs beyond their canonical roles, uncovering non-canonical functions in protein secretion and the identification of snoRNA/scaRNA reads within glycoRNA-associated small RNA populations, suggesting novel mechanisms of cellular communication and pathophysiology. This review offers an integrative discussion of snoRNAs, focusing on their biogenesis, functions, developmental roles, and implications in various diseases, while providing detailed insights into these RNAs.