Small nucleolar RNA
Small nucleolar RNA (snoRNA) is a class of small RNA molecules that primarily guide chemical modifications of other RNAs, such as ribosomal RNA, transfer RNA, and other small nuclear RNAs. These modifications include 2'-O-ribose methylation and pseudouridylation, which are critical for the proper functioning of these RNAs. SnoRNAs are found within the nucleolus of the cell, a substructure where ribosome assembly occurs, hence their name. They are also found in other parts of the cell, including the nucleoplasm. There are two main families of snoRNAs: C/D box snoRNAs, which are involved in methylation, and H/ACA box snoRNAs, which are involved in pseudouridylation.
Classification
SnoRNAs are classified into two main families based on conserved sequence motifs and structural features:
- C/D box snoRNAs: Characterized by the presence of C (RUGAUGA) and D (CUGA) box motifs. These snoRNAs guide 2'-O-ribose methylation of target RNAs.
- H/ACA box snoRNAs: Characterized by the presence of H (ANANNA) and ACA box motifs. These snoRNAs guide the conversion of uridine to pseudouridine in target RNAs.
Function
The primary function of snoRNAs is to guide the chemical modification of other RNA molecules, enhancing their stability and function. These modifications are crucial for the proper assembly and function of the ribosome, the cellular machinery responsible for protein synthesis. SnoRNAs recognize specific sequences on target RNAs through base pairing, directing the modification enzymes to the correct site.
Biogenesis and Localization
SnoRNAs are typically encoded within the introns of host genes and are released by splicing. They are then transported to the nucleolus, where they associate with specific proteins to form small nucleolar ribonucleoproteins (snoRNPs). These complexes are responsible for the enzymatic activity associated with RNA modification.
Role in Disease
Alterations in snoRNA expression and function have been implicated in various human diseases, including cancer, Prader-Willi syndrome, and dyskeratosis congenita. These associations highlight the importance of snoRNAs in maintaining cellular homeostasis and the potential for targeting snoRNA pathways in disease treatment.
Research and Applications
Research on snoRNAs has expanded our understanding of RNA-based regulatory mechanisms and their impact on gene expression and cellular function. SnoRNAs also present potential targets for therapeutic intervention in diseases associated with RNA dysfunction.
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Contributors: Prab R. Tumpati, MD