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Review
. 2024 Jun 29;25(13):7202.
doi: 10.3390/ijms25137202.

SnoRNAs: Exploring Their Implication in Human Diseases

Waseem Chauhan  1 , Sudharshan Sj  1 , Sweta Kafle  1 , Rahima Zennadi  1
Affiliations
Review

SnoRNAs: Exploring Their Implication in Human Diseases

Waseem Chauhan et al. Int J Mol Sci. .

Abstract

Small nucleolar RNAs (snoRNAs) are earning increasing attention from research communities due to their critical role in the post-transcriptional modification of various RNAs. These snoRNAs, along with their associated proteins, are crucial in regulating the expression of a vast array of genes in different human diseases. Primarily, snoRNAs facilitate modifications such as 2'-O-methylation, N-4-acetylation, and pseudouridylation, which impact not only ribosomal RNA (rRNA) and their synthesis but also different RNAs. Functionally, snoRNAs bind with core proteins to form small nucleolar ribonucleoproteins (snoRNPs). These snoRNAs then direct the protein complex to specific sites on target RNA molecules where modifications are necessary for either standard cellular operations or the regulation of pathological mechanisms. At these targeted sites, the proteins coupled with snoRNPs perform the modification processes that are vital for controlling cellular functions. The unique characteristics of snoRNAs and their involvement in various non-metabolic and metabolic diseases highlight their potential as therapeutic targets. Moreover, the precise targeting capability of snoRNAs might be harnessed as a molecular tool to therapeutically address various disease conditions. This review delves into the role of snoRNAs in health and disease and explores the broad potential of these snoRNAs as therapeutic agents in human pathologies.

Keywords: RNA processing; human pathologies; small non-coding nucleolar RNA; small nucleolar ribonucleoproteins; snoRNA biogenesis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Diagrammatic representation of snoRNA biogenesis. (A) After the transcription process, newly formed mRNA undergoes a splicing process to remove the introns. (B,C) These introns undergo further nucleolytic processing, then lariat structure formation evolves as either C/D box snoRNAs or H/ACA snoRNAs. (C) The snoRNAs specifically bind to the SNU13 (aka 15.5K), NOP56, NOP58 and FBL proteins to become C/D box snoRNPs, while the assembly of H/ACA snoRNPs involves core proteins such as Nap57, Cbf5p (dyskerin), and GAR1.
Figure 2
Figure 2
Depicting H/ACA snoRNP modifying various RNAs. (A,G) The H/ACA box snoRNP formed after the snoRNA is associated with multiple proteins (e.g., Nhp2, Nop10, Dyskerin and Gar1), are actively involved in the modification of various RNAs (miRNA, tRNA, mRNA, rRNA or/and sdRNA). (B,C) These H/ACA box snoRNAs are also involved in modifications (N4-acetylation, 2′-O-methylation and Pseudouridylation) on rRNA, and then help in the biogenesis of ribosomes. (D) Alternative splicing of mRNA is one of the important functions of these snoRNAs as well. (E,F) These H/ACA box snoRNAs are in addition actively involved in the pseudouridylation of mRNAs and tRNAs and help in their maturation.
Figure 3
Figure 3
Box C/D snoRNA-guided 2′-O-methylation of various RNAs. Once the box C/D snoRNAs are bound to the SNU13 (aka 15.5K), NOP56, NOP58 and FBL proteins to become C/D box snoRNPs, these proteins are guided by snoRNAs to target RNAs and bind to a complementary sequence on the RNA target through a short antisense element. The RNA target then undergoes 2′-O-methylation at a specific site mediated by FBL. Nm modification occurs on various RNA types.
Figure 4
Figure 4
Acetylation of 18S ribosomal RNA. Acetylation is one of the other important modifications required for the proper assembly of the ribosome or ribosomal biogenesis. In this figure, it is evident that snoRNA makes the Watson–Crick base pairing with 18S rRNA but prior to the interaction with RNA acetyltransferase. RNA acetyltansferase helps then the 18S rRNA to be navigated, prior to acetylate cytidine residues.
Figure 5
Figure 5
snoRNAs with associated proteins participate in multiple cellular functions including cell proliferation in AML. (A) AML cells lack SNORA21 and thereby do not show pseudouridylation that hampered the ribosomal synthesis needed for regulatory proteins. (B) AML cells also show chromosomal translocation t(8;21) causing chimeric protein (AML1-ETO) formation. AES shows oncogenic activity of this chimeric protein after the association with snoRNPs via interaction with DDX21. (C) Approximately, 30% of AML patients shows frameshift mutation in nucleophosmin (NPM1) protein, B23, which is destined to be in the nucleus but after frameshift mutation, B23 protein localizes in the cytosol. Thus, without B23 protein in the nucleus, C/D box RNPs are unable to process modification of the mRNA and chromatin remodeling.
Figure 6
Figure 6
Figure representing the anti-cancerous nature of some snoRNAs. In hepatoblastoma, SNORA14A (H/ACA box snoRNA) is overexpressed and enhanced the ribosomal biogenesis required for the expression of succinate dehydrogenase subunit B (SDSB) protein. SDSB can reduce the cellular proliferation and exerts apoptotic effects in hepatoblastoma cells. Similarly, the C/D box snoRNAs, SNORD76 and SNORD44, also exhibit antiproliferative effect in multiple cancers.
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