Small Nucleolar RNAs as Diagnostic and Prognostic Biomarkers in Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Small nucleolar RNAs (snoRNAs) form clusters within the genome, representing a mysterious category of small non-coding RNAs. Research has demonstrated that aberrant snoRNAs can contribute to the development of various types of cancers. Recent studies have identified snoRNAs as potentially valuable biomarkers for the diagnosis or/and prognosis of cancers. However, there has been a lack of comprehensive reviews on prognostic and diagnostic snoRNAs across different types of cancers. METHODS: We conducted a systematic search of various databases including Google Scholar, Medline, Cochrane, Scopus, PubMed, Embase, ScienceDirect, Ovid-Medline, Chinese National Knowledge Infrastructure, WanFang, and SinoMed with a time frame reception to December 30, 2022. A total of 49 relevant articles were included in our analysis, consisting of 21 articles focusing on diagnostic aspects and 41 articles focusing on prognostic aspects. Pooled odds ratio, 95% confidence intervals (CIs), and hazard ratio (HR) were utilized to evaluate clinical parameters and overall survival (OS), respectively. RESULT: The findings indicated that area under the curve, sensitivity, and specificity were 0.85, 75%, and 80% in cancer, respectively. There was a possibility that snoRNAs had a positive impact on the diagnosis (risk ratio, RR = 2.95, 95% CI: 2.75-3.16, P = 0.000) and OS (HR = 1) in cancer. Additionally, abnormally expressed snoRNAs were associated with a positive impact on OS time for chronic lymphocytic leukemia (HR: 0.88, 95%Cl: 0.69-1.11, P < 0.00001), colon adenocarcinoma (HR: 0.97, 95%Cl: 0.91-1.03, P < 0.0001), and ovarian cancer (HR: 0.98, 95%Cl: 0.98-0.99, P < 0.00001). However, dysregulated snoRNAs of colon cancer and colorectal cancer had a negative impact on OS time (HR = 3.01 and 1.01 respectively, P < 0.0001). CONCLUSION: The results strongly suggested that snoRNAs could serve as potential novel indicators for prognosis and diagnosis in cancers. This systematic review followed the guidelines of the Transparent Reporting of Systematic Review and Meta-Analyses (PROSPERO register: CRD42020209096).

Loss of Conserved rRNA Modifications in the Peptidyl Transferase Center Leads to Diminished Protein Synthesis and Cell Growth in Budding Yeast.

Ribosomal RNAs (rRNAs) are extensively modified during the transcription and subsequent maturation. Three types of modifications, 2'-O-methylation of ribose moiety, pseudouridylation, and base modifications, are introduced either by a snoRNA-driven mechanism or by stand-alone enzymes. Modified nucleotides are clustered at the functionally important sites, including peptidyl transferase center (PTC). Therefore, it has been hypothesised that the modified nucleotides play an important role in ensuring the functionality of the ribosome. In this study, we demonstrate that seven 25S rRNA modifications, including four evolutionarily conserved modifications, in the proximity of PTC can be simultaneously depleted without loss of cell viability. Yeast mutants lacking three snoRNA genes (snR34, snR52, and snR65) and/or expressing enzymatically inactive variants of spb1(D52A/E679K) and nop2(C424A/C478A) were constructed. The results show that rRNA modifications in PTC contribute collectively to efficient translation in eukaryotic cells. The deficiency of seven modified nucleotides in 25S rRNA resulted in reduced cell growth, cold sensitivity, decreased translation levels, and hyperaccurate translation, as indicated by the reduced missense and nonsense suppression. The modification m5C2870 is crucial in the absence of the other six modified nucleotides. Thus, the pattern of rRNA-modified nucleotides around the PTC is essential for optimal ribosomal translational activity and translational fidelity.

U3 snoRNA inter-regulates with DDX21 in the perichromosomal region to control mitosis.

U3 snoRNA is essential for ribosome biogenesis during interphase. Upon mitotic onset, the nucleolus disassembles and U3 snoRNA relocates to the perichromosomal region (PR) to be considered as a chromosome passenger. Whether U3 controls mitosis remains unknown. Here, we demonstrate that U3 snoRNA is required for mitotic progression. We identified DDX21 as the predominant U3-binding protein during mitosis and confirmed that U3 snoRNA colocalizes with DDX21 in the PR. DDX21 knockdown induces mitotic catastrophe and similar mitotic defects caused by U3 snoRNA depletion. Interestingly, the uniform PR distribution of U3 snoRNA and DDX21 is interdependent. DDX21 functions in mitosis depending on its PR localization. Mechanistically, U3 snoRNA regulates DDX21 PR localization through maintaining its mobility. Moreover, Cy5-U3 snoRNA downsizes the fibrous condensates of His-DDX21 at proper molecular ratios in vitro. This work highlights the importance of the equilibrium between U3 snoRNA and DDX21 in PR formation and reveals the potential relationship between the PR assembly and mitotic regulation.

Role of small nucleolar RNAs in alternative splicing of the doublesex gene in the silkworm, Bombyx mori.

More and more evidence shows that small noncoding RNAs (ncRNAs) play diverse roles in development, stress response and other cellular processes, but functional study of intermediate-size ncRNAs is still rare. Here, the expression profile of 16 intermediate-size ncRNAs in ovary and testis of silkworm Bombyx mori were analyzed. Twelve ncRNAs, including 5 small nucleolar RNAs (snoRNAs) and 7 unclassified ncRNAs, accumulated more in the testis than in the ovary of silkworm, especially Bm-163, Bm-51 and Bm-68. Four ncRNAs (including three orphan snoRNAs and one unclassified ncRNA) had higher expression level in the ovary than in the testis, especially Bm-86. Overexpression of the testis-enriched snoRNA Bm-68 in the female led to the accumulation of male-specific isoform of doublesex (BmdsxM) and increased the expression ratio of BmdsxM: BmdsxF. While overexpression of ovary-enriched snoRNA Bm-86 in the male decreased the expression ratio of BmdsxM: BmdsxF, indicating the roles of the two snoRNAs played in the alternative splicing of Bmdsx of silkworm, which will provide new clues for the functional study of snoRNAs in insects.

Identification of novel snoRNA-based biomarkers for clear cell renal cell carcinoma from urine-derived extracellular vesicles.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC with high rates of metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects and tumor recurrence remain a challenge. As a result, ccRCC still have a high mortality rate. Early detection before metastasis has great potential to improve outcomes, but no suitable biomarker specific for ccRCC is available so far. Therefore, molecular biomarkers derived from body fluids have been investigated over the past decade. Among them, RNAs from urine-derived extracellular vesicles (EVs) are very promising. METHODS: RNA was extracted from urine-derived EVs from a cohort of 78 subjects (54 ccRCC patients, 24 urolithiasis controls). RNA-seq was performed on the discovery cohort, a subset of the whole cohort (47 ccRCC, 16 urolithiasis). Reads were then mapped to the genome, and expression was quantified based on 100 nt long contiguous genomic regions. Cluster analysis and differential region expression analysis were performed with adjustment for age and gender. The candidate biomarkers were validated by qPCR in the entire cohort. Receiver operating characteristic, area under the curve and odds ratios were used to evaluate the diagnostic potential of the models. RESULTS: An initial cluster analysis of RNA-seq expression data showed separation by the subjects' gender, but not by tumor status. Therefore, the following analyses were done, adjusting for gender and age. The regions differentially expressed between ccRCC and urolithiasis patients mainly overlapped with small nucleolar RNAs (snoRNAs). The differential expression of four snoRNAs (SNORD99, SNORD22, SNORD26, SNORA50C) was validated by quantitative PCR. Confounder-adjusted regression models were then used to classify the validation cohort into ccRCC and tumor-free subjects. Corresponding accuracies ranged from 0.654 to 0.744. Models combining multiple genes and the risk factors obesity and hypertension showed improved diagnostic performance with an accuracy of up to 0.811 for SNORD99 and SNORA50C (p = 0.0091). CONCLUSIONS: Our study uncovered four previously unrecognized snoRNA biomarkers from urine-derived EVs, advancing the search for a robust, easy-to-use ccRCC screening method.

HMGB1 prefers to interact with structural RNAs and regulates rRNA methylation modification and translation in HeLa cells.

BACKGROUND: High-mobility group B1 (HMGB1) is both a DNA binding nuclear factor modulating transcription and a crucial cytokine that mediates the response to both infectious and noninfectious inflammation such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. HMGB1 has been proposed to control ribosome biogenesis, similar as the other members of a class of HMGB proteins. RESULTS: Here, we report that HMGB1 selectively promotes transcription of genes involved in the regulation of transcription, osteoclast differentiation and apoptotic process. Improved RNA immunoprecipitation by UV cross-linking and deep sequencing (iRIP-seq) experiment revealed that HMGB1 selectively bound to mRNAs functioning not only in signal transduction and gene expression, but also in axon guidance, focal adhesion, and extracellular matrix organization. Importantly, HMGB1-bound reads were strongly enriched in specific structured RNAs, including the domain II of 28S rRNA, H/ACA box snoRNAs including snoRNA63 and scaRNAs. RTL-P experiment showed that overexpression of HMGB1 led to a decreased methylation modification of 28S rRNA at position Am2388, Cm2409, and Gm2411. We further showed that HMGB1 overexpression increased ribosome RNA expression levels and enhanced protein synthesis. CONCLUSION: Taken together, our results support a model in which HMGB1 binds to multiple RNA species in human cancer cells, which could at least partially contribute to HMGB1-modulated rRNA modification, protein synthesis function of ribosomes, and differential gene expression including rRNA genes. These findings provide additional mechanistic clues to HMGB1 functions in cancers and cell differentiation.

Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients.

Deregulation of small non-coding RNAs (sncRNAs) has been associated with the onset of metastasis. We evaluated the expression of sncRNAs in patients with early-stage breast cancer, performing RNA sequencing in 60 patients for whom tumor and sentinel lymph node (SLN) samples were available, and conducting differential expression, gene ontology, enrichment and survival analyses. Sequencing annotation classified most of the sncRNAs into small nucleolar RNA (snoRNAs, 70%) and small nuclear RNA (snRNA, 13%). Our results showed no significant differences in sncRNA expression between tumor or SLNs obtained from the same patient. Differential expression analysis showed down-regulation (n = 21) sncRNAs and up-regulation (n = 2) sncRNAs in patients with locoregional metastasis. The expression of SNHG5, SNORD90, SCARNA2 and SNORD78 differentiated luminal A from luminal B tumors, whereas SNORD124 up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (SNORD93, SNORA16A, SNORD113-6, SNORA7A, SNORA57 and SNORA18A) that distinguished patients with locoregional metastasis and predicted patient outcome. Gene ontology and Reactome pathway analysis showed an enrichment of biological processes associated with translation initiation, protein targeting to specific cell locations, and positive regulation of Wnt and NOTCH signaling pathways, commonly involved in the promotion of metastases. Our results point to the potential of several sncRNAs as surrogate markers of lymph node metastases and patient outcome in early-stage breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant sncRNAs and to validate our results in a larger cohort of patients.

SNORA69 is up-regulated in the lateral habenula of individuals with major depressive disorder.

Major depressive disorder (MDD) is a complex and potentially debilitating illness whose etiology and pathology remains unclear. Non-coding RNAs have been implicated in MDD, where they display differential expression in the brain and the periphery. In this study, we quantified small nucleolar RNA (snoRNA) expression by small RNA sequencing in the lateral habenula (LHb) of individuals with MDD (n = 15) and psychiatrically-healthy controls (n = 15). We uncovered five snoRNAs that exhibited differential expression between MDD and controls (FDR < 0.01). Specifically, SNORA69 showed increased expression in MDD and was technically validated via RT-qPCR. We further investigated the expression of Snora69 in the LHb and peripheral blood of an unpredicted chronic mild stress (UCMS) mouse model of depression. Snora69 was specifically up-regulated in mice that underwent the UCMS paradigm. SNORA69 is known to guide pseudouridylation onto 5.8S and 18S rRNAs. We quantified the relative abundance of pseudouridines on 5.8S and 18S rRNA in human post-mortem LHb samples and found increased abundance of pseudouridines in the MDD group. Overall, our findings indicate the importance of brain snoRNAs in the pathology of MDD. Future studies characterizing SNORA69's role in MDD pathology is warranted.

IGCNSDA: unraveling disease-associated snoRNAs with an interpretable graph convolutional network.

Accurately delineating the connection between short nucleolar RNA (snoRNA) and disease is crucial for advancing disease detection and treatment. While traditional biological experimental methods are effective, they are labor-intensive, costly and lack scalability. With the ongoing progress in computer technology, an increasing number of deep learning techniques are being employed to predict snoRNA-disease associations. Nevertheless, the majority of these methods are black-box models, lacking interpretability and the capability to elucidate the snoRNA-disease association mechanism. In this study, we introduce IGCNSDA, an innovative and interpretable graph convolutional network (GCN) approach tailored for the efficient inference of snoRNA-disease associations. IGCNSDA leverages the GCN framework to extract node feature representations of snoRNAs and diseases from the bipartite snoRNA-disease graph. SnoRNAs with high similarity are more likely to be linked to analogous diseases, and vice versa. To facilitate this process, we introduce a subgraph generation algorithm that effectively groups similar snoRNAs and their associated diseases into cohesive subgraphs. Subsequently, we aggregate information from neighboring nodes within these subgraphs, iteratively updating the embeddings of snoRNAs and diseases. The experimental results demonstrate that IGCNSDA outperforms the most recent, highly relevant methods. Additionally, our interpretability analysis provides compelling evidence that IGCNSDA adeptly captures the underlying similarity between snoRNAs and diseases, thus affording researchers enhanced insights into the snoRNA-disease association mechanism. Furthermore, we present illustrative case studies that demonstrate the utility of IGCNSDA as a valuable tool for efficiently predicting potential snoRNA-disease associations. The dataset and source code for IGCNSDA are openly accessible at: https://github.com/altriavin/IGCNSDA.

The regulatory roles of small nucleolar RNAs within their host locus.

Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides this canonical role, several snoRNAs are now known to regulate diverse levels of gene expression. While these functions are carried out in trans by mature snoRNAs, evidence has also been emerging of regulatory roles of snoRNAs in cis, either within their genomic locus or as longer transcription intermediates during their maturation. Herein, we review recent findings that snoRNAs can interact in cis with their intron to regulate the expression of their host gene. We also explore the ever-growing diversity of longer host-derived snoRNA extensions and their functional impact across the transcriptome. Finally, we discuss the role of snoRNA duplications into forging these new layers of snoRNA-mediated regulation, as well as their involvement in the genomic imprinting of their host locus.

Subverting the Canon: Novel Cancer-Promoting Functions and Mechanisms for snoRNAs.

Small nucleolar RNAs (snoRNAs) constitute a class of intron-derived non-coding RNAs ranging from 60 to 300 nucleotides. Canonically localized in the nucleolus, snoRNAs play a pivotal role in RNA modifications and pre-ribosomal RNA processing. Based on the types of modifications they involve, such as methylation and pseudouridylation, they are classified into two main families-box C/D and H/ACA snoRNAs. Recent investigations have revealed the unconventional synthesis and biogenesis strategies of snoRNAs, indicating their more profound roles in pathogenesis than previously envisioned. This review consolidates recent discoveries surrounding snoRNAs and provides insights into their mechanistic roles in cancer. It explores the intricate interactions of snoRNAs within signaling pathways and speculates on potential therapeutic solutions emerging from snoRNA research. In addition, it presents recent findings on the long non-coding small nucleolar RNA host gene (lncSNHG), a subset of long non-coding RNAs (lncRNAs), which are the transcripts of parental SNHGs that generate snoRNA. The nucleolus, the functional epicenter of snoRNAs, is also discussed. Through a deconstruction of the pathways driving snoRNA-induced oncogenesis, this review aims to serve as a roadmap to guide future research in the nuanced field of snoRNA-cancer interactions and inspire potential snoRNA-related cancer therapies.

NAP-seq reveals multiple classes of structured noncoding RNAs with regulatory functions.

Up to 80% of the human genome produces "dark matter" RNAs, most of which are noncapped RNAs (napRNAs) that frequently act as noncoding RNAs (ncRNAs) to modulate gene expression. Here, by developing a method, NAP-seq, to globally profile the full-length sequences of napRNAs with various terminal modifications at single-nucleotide resolution, we reveal diverse classes of structured ncRNAs. We discover stably expressed linear intron RNAs (sliRNAs), a class of snoRNA-intron RNAs (snotrons), a class of RNAs embedded in miRNA spacers (misRNAs) and thousands of previously uncharacterized structured napRNAs in humans and mice. These napRNAs undergo dynamic changes in response to various stimuli and differentiation stages. Importantly, we show that a structured napRNA regulates myoblast differentiation and a napRNA DINAP interacts with dyskerin pseudouridine synthase 1 (DKC1) to promote cell proliferation by maintaining DKC1 protein stability. Our approach establishes a paradigm for discovering various classes of ncRNAs with regulatory functions.

Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer.

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

2'-O-ribose methylation levels of ribosomal RNA distinguish different types of growth arrest in human dermal fibroblasts.

The 2'-O-methylation (2'-O-Me) of ribosomal RNA (rRNA) shows plasticity that is potentially associated with cell phenotypes. We used RiboMeth-seq profiling to reveal growth arrest-specific 2'-O-Me patterns in primary human dermal fibroblasts from three different donors. We exposed cells to hydrogen peroxide to induce cellular senescence and to high cell densities to promote quiescence by contact inhibition. We compared both modes of cell cycle arrest to proliferating cells and could indeed distinguish these conditions by their overall 2'-O-Me patterns. Methylation levels at a small fraction of sites showed plasticity and correlated with the expression of specific small nucleolar RNAs (snoRNAs) but not with expression of fibrillarin. Moreover, we observed subtle senescence-associated alterations in ribosome biogenesis. Knockdown of the snoRNA SNORD87, which acts as a guide for modification of a hypermethylated position in non-proliferating cells, was sufficient to boost cell proliferation. Conversely, depletion of SNORD88A, SNORD88B and SNORD88C, which act as guides for modification of a hypomethylated site, caused decreased proliferation without affecting global protein synthesis or apoptosis. Taken together, our findings provide evidence that rRNA modifications can be used to distinguish and potentially influence specific growth phenotypes of primary cells.

The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

Long non-coding RNA small nucleolar RNA host gene 29 drives chronic myeloid leukemia progression via microRNA-483-3p/Casitas B-lineage Lymphoma axis-mediated activation of the phosphoinositide 3-kinase/Akt pathway.

The aberrant expression of the long non-coding RNA (lncRNA) Small Nucleolar RNA Host Gene 29 (SNHG29) has been associated with various human cancers. However, the role of SNHG29 in chronic myeloid leukemia (CML) remains elusive. Therefore, this study aimed to investigate the function of SNHG29 in CML and unveil its potential underlying mechanisms. Herein, peripheral blood samples from 44 CML patients and 17 healthy subjects were collected. The expressions of SNHG29, microRNA-483-3p (miR-483-3p), and Casitas B-lineage Lymphoma (CBL) were measured using quantitative polymerase chain reaction (qPCR) or Western Blot. Cell viability, apoptosis, and cell cycle progression were evaluated using the Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine incorporation, and flow cytometry, respectively. Western Blot analysis was employed to assess protein expressions related to cellular proliferation, apoptosis, and oncogenesis. RNA immunoprecipitation and dual-luciferase reporter assays were utilized to verify the interactions among SNHG29, miR-483-3p, and CBL. SNHG29 was significantly overexpressed in both blood samples of CML patients and CML cell lines. In CML, increased expression of SNHG29 was positively correlated with clinical staging, and patients with high SNHG29 expression had poorer survival outcomes. Functionally, knocking down SNHG29 effectively inhibited CML cell proliferation and promoted apoptosis. Mechanistically, SNHG29 acted as a competing endogenous RNA for miR-483-3p to modulate CBL expression, thereby activating the Phosphoinositide 3-Kinase/Akt signaling pathway and mediating CML progression. In summary, these findings reveal that SNHG29 promotes tumorigenesis in CML, offering a potential therapeutic strategy for CML treatment.

Small nucleolar RNA Snora73 promotes psoriasis progression by sponging miR-3074-5p and regulating PBX1 expression.

Chronic psoriasis is a kind of immune-mediated skin illness and the underlying molecular mechanisms of pathogenesis remain incompletely understood. Here, we used small RNA microarray assays to scan the differential expressed RNAs in psoriasis patient samples. The downstream miRNAs and its targets were predicted using bioinformatics analysis from online bases and confirmed using fluorescence in situ hybridization and dual­luciferase report gene assay. Cell ability of proliferation and migration were detected using CCK-8 and transwell assays. The results showed that a new snoRNA Snora73 was upregulated in psoriasis patient samples. Overexpression of Snora73 significantly increased psoriasis cells viability and migration, while knockdown of Snora73 got the opposite results. Mechanistically, our results showed that Snora73 acted as a sponge for miR-3074-5p and PBX1 is a direct target of miR-3074-5p in psoriasis cells. Furthermore, miR-3074-5p suppressed psoriasis cell proliferation and migration, while PBX1 promoted cell proliferation and migration in psoriasis. Collectively, these findings reveal a crucial role of Snora73 in progression of psoriasis through miR-3074-5p/PBX1 signaling pathway and suggest a potential therapeutic strategy.

Emerging roles of SnoRNAs in the pathogenesis and treatment of autoimmune disorders.

SnoRNAs (small non-coding RNAs) have recently gained prominence in autoimmune diseases, revealing their crucial role in modulating the immune response and contributing to disease pathogenesis. Initially known for their involvement in ribosomal RNA processing and modification, molecular biology and genomics advancements have uncovered their broader impact on cellular function, especially in autoimmune disorders. Autoimmune diseases represent conditions characterized by the immune system's erroneous attacks on self-tissues, encompassing disorders like systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The complex etiology of these conditions involves a delicate interplay of genetic and environmental factors. Emerging evidence suggests that snoRNAs initially recognized for their housekeeping roles, extend their influence on immune regulation through diverse mechanisms. SnoRNAs have been implicated in epigenetic modification, directly affecting the gene expression profiles of immune cells. Their ability to guide site-specific changes on ribosomal RNAs and other non-coding RNAs can significantly influence the translation of proteins involved in immune response pathways. Moreover, snoRNAs interact with key immune-related proteins, modulating their functions and subsequently impacting immune cell development, activation, and tolerance. Dysregulation of snoRNA expression has been observed in various autoimmune diseases, underscoring their potential as biomarkers for disease diagnosis, prognosis, and therapeutic targets. Manipulating snoRNA expression or activity is a promising therapeutic intervention avenue, offering the potential for personalized treatment strategies in autoimmune diseases. However, there remains a need for comprehensive research efforts to elucidate the precise molecular mechanisms underlying snoRNA-mediated immune modulation. Further investigations in this domain are essential to unravel the potential of snoRNAs in autoimmune disorders.

The Efg1-Bud22 dimer associates with the U14 snoRNP contacting the 5' rRNA domain of an early 90S pre-ribosomal particle.

The DEAD-box helicase Dbp4 plays an essential role during the early assembly of the 40S ribosome, which is only poorly understood to date. By applying the yeast two-hybrid method and biochemical approaches, we discovered that Dbp4 interacts with the Efg1-Bud22 dimer. Both factors associate with early pre-90S particles and smaller complexes, each characterized by a high presence of the U14 snoRNA. A crosslink analysis of Bud22 revealed its contact to the U14 snoRNA and the 5' domain of the nascent 18S rRNA, close to its U14 snoRNA hybridization site. Moreover, depletion of Bud22 or Efg1 specifically affects U14 snoRNA association with pre-ribosomal complexes. Accordingly, we concluded that the role of the Efg1-Bud22 dimer is linked to the U14 snoRNA function on early 90S ribosome intermediates chaperoning the 5' domain of the nascent 18S rRNA. The successful rRNA folding of the 5' domain and the release of Efg1, Bud22, Dpb4, U14 snoRNA and associated snoRNP factors allows the subsequent recruitment of the Kre33-Bfr2-Enp2-Lcp5 module towards the 90S pre-ribosome.

Characterization the prognosis role and effects of snoRNAs in melanoma patients.

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.