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Small RNAs derived from snoRNAs.

ABSTRACT: Small nucleolar RNAs (snoRNAs) guide RNA modification and are localized in nucleoli and Cajal bodies in eukaryotic cells. Components of the RNA silencing pathway associate with these structures, and two recent reports have revealed that a human and a protozoan snoRNA can be processed into miRNA-like RNAs. Here we show that small RNAs with evolutionary conservation of size and position are derived from the vast majority of snoRNA loci in animals (human, mouse, chicken, fruit fly), Arabidopsis, and fission yeast. In animals, sno-derived RNAs (sdRNAs) from H/ACA snoRNAs are predominantly 20-24 nucleotides (nt) in length and originate from the 3' end. Those derived from C/D snoRNAs show a bimodal size distribution at approximately 17-19 nt and >27 nt and predominantly originate from the 5' end. SdRNAs are associated with AGO7 in Arabidopsis and Ago1 in fission yeast with characteristic 5' nucleotide biases and show altered expression patterns in fly loquacious and Dicer-2 and mouse Dicer1 and Dgcr8 mutants. These findings indicate that there is interplay between the RNA silencing and snoRNA-mediated RNA processing systems, and that sdRNAs comprise a novel and ancient class of small RNAs in eukaryotes.

SUBMITTER: Taft RJ

PROVIDER: S-EPMC2704076 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Small RNAs derived from snoRNAs.

Taft Ryan J RJ Glazov Evgeny A EA Lassmann Timo T Hayashizaki Yoshihide Y Carninci Piero P Mattick John S JS

RNA (New York, N.Y.) 20090527 7

Small nucleolar RNAs (snoRNAs) guide RNA modification and are localized in nucleoli and Cajal bodies in eukaryotic cells. Components of the RNA silencing pathway associate with these structures, and two recent reports have revealed that a human and a protozoan snoRNA can be processed into miRNA-like RNAs. Here we show that small RNAs with evolutionary conservation of size and position are derived from the vast majority of snoRNA loci in animals (human, mouse, chicken, fruit fly), Arabidopsis, an ...[more]

PMID: 19474147

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Project description:Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction. A comprehensive analysis was performed to select significant survival‐related snoRNAs in DLBCL. Collectively, a prognostic signature based on three snoRNAs (SNORD1A, SNORA60, and SNORA66) was established for DLBCL patients. Also, we found snoRNA co‐expressed genes that were mostly involved in ribosome‐correlated pathways and processes, and the interaction of ribosomal proteins (RPL23, RPL10A) and p53.

Project description:tRNA‑derived small RNAs (tsRNAs) have been shown to play regulatory roles in many physiological and pathological processes. However, their roles in hypertrophic scars remain unclear. The present study investigated differentially expressed tsRNAs in human hypertrophic scar fibroblasts and normal skin fibroblasts via high‑throughput sequencing. Several dysregulated tsRNAs were validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, target prediction, coexpression networks and competing endogenous RNA (ceRNA) networks were evaluated to discover the principal functions of significantly differentially expressed tsRNAs. In total, 67 differentially expressed tsRNAs were detected, of which 27 were upregulated and 40 downregulated in hypertrophic scar fibroblasts. The GO analysis indicated that the dysregulated tsRNAs are associated with numerous biological functions, including 'nervous system development', 'cell adhesion', 'focal adhesion', 'protein binding', 'angiogenesis' and 'actin binding'. KEGG pathway analysis revealed that the most altered pathways include 'Ras signaling pathway', 'Rap1 signaling pathway' and 'cGMP‑PKG signaling pathway'. The target genes of the differentially expressed tsRNAs participate in several signaling pathways important for scar formation. The results of RT‑qPCR were consistent with those of sequencing. MicroRNA (miR)‑29b‑1‑5p was identified as a target of tsRNA‑23678 and was downregulated in hypertrophic scar fibroblasts, constituting a negative regulatory factor for scar formation. Furthermore, tsRNA‑23761 acted as a ceRNA and bound to miR‑3135b to regulate the expression of miR‑3135b targets, including angiotensin‑converting enzyme. Collectively, these findings reveal that tsRNAs are differentially expressed in human hypertrophic scar fibroblasts, and may contribute to the molecular mechanism and treatment of hypertrophic scars.

Dataset Information

Small RNAs derived from snoRNAs.

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Small RNAs derived from snoRNAs.

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