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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing

ABSTRACT: Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing

PROVIDER: PRJNA590255 | ENA |

REPOSITORIES: ENA

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Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano77]

Project description:H/ACA small nucleolar RNAs (snoRNAs) guide pseudouridylation as part of a small nucleolar ribonucleoprotein complex (snoRNP). Disruption of H/ACA snoRNA expression in stem cells impairs pluripotency, yet it remains unclear how H/ACA snoRNAs contribute to differentiation. To determine if H/ACA snoRNA expression is dynamic during differentiation, we comprehensively profiled H/ACA snoRNA expression in multiple murine cell types and during differentiation in three cellular models, including mouse embryonic stem cells and mouse myoblasts. We determined that H/ACA snoRNA expression is cell-type specific, and we identified a subset of snoRNAs that are specifically regulated during differentiation. Additionally, we demonstrated that a decrease in Snora27 expression upon differentiation corresponds to a decrease in pseudouridylation of its target site within the E-site transfer RNA (tRNA) binding region of the 28S ribosomal RNA (rRNA) in the large ribosomal subunit. Many of the snoRNAs regulated during differentiation have target nucleotides in the 28S rRNA, and we found that pre-rRNA processing of large subunit precursors is altered during differentiation. Together, these data suggest a model in which H/ACA snoRNAs are specifically regulated during differentiation to potentially alter pseudouridylation and fine tune ribosome function.

2020-07-09 | GSE140622 | GEO

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano104]

2020-07-09 | GSE140618 | GEO

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [RNA-seq and ncRNA-seq]

2020-07-09 | GSE139812 | GEO

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano77]

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano77]

| PRJNA590261 | ENA

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano104]

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [Nano104]

| PRJNA590252 | ENA

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [RNA-seq and ncRNA-seq]

Project description:Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing [RNA-seq and ncRNA-seq]

| PRJNA587069 | ENA

A systematic dissection of determinants and consequences of snoRNA-guided pseudouridylation of human mRNA

Project description:RNA can be extensively modified post-transcriptionally with >170 covalent modifications, expanding its functional and structural repertoire. Pseudouridine (Ψ), the most abundant modified nucleoside in rRNA and tRNA, has recently been found within mRNA molecules. Due to technical challenges, it remained unclear whether pseudouridylation of mRNA can be snoRNA-guided, which has important implications for understanding the physiological target spectrum of snoRNAs and for their potential therapeutic exploitation in genetic diseases. Here, using a massively parallel reporter based strategy we simultaneously interrogate Ψ levels across hundreds of synthetic constructs with predesigned complementarity against endogenous snoRNAs. Our results demonstrate that snoRNA-mediated pseudouridylation can occur on mRNA targets. However, this is typically achieved at low efficiencies, and is constrained by the localization of mRNA, by the expression levels of snoRNAs and by the length of the snoRNA:mRNA complementarity stretches. We exploited these insights for the design of snoRNAs targeting pseudouridylation at premature termination codons, which was previously suggested to suppress translational termination. However, in contrast to previous studies, in this and follow-up experiments we observe no evidence for readthrough of pseudouridylated stop codons. Our study enhances our understanding of the scope, ‘design rules’ and constraints of snoRNA-mediated pseudouridylation, and challenges a key functional outcome associated with this modification.

2024-06-02 | GSE159749 | GEO

Regulated snoRNA expression during differentiation corresponds with a change in ribosomal RNA pseudouridylation and altered pre-ribosomal RNA processing

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-09 | GSE140623 | GEO

Atypical U3 snoRNA Suppresses the Process of Pterygia through Modulating 18S Ribosomal RNA Synthesis

Project description:Ribosome biosynthesis plays a crucial role in regulating protein translation and is essential for cell growth and development in physiological progress. The progression and recurrence of Pterygia mainly occur due to the abnormal proliferation and migration of stromal Pterygia fibroblasts. Small nucleolar RNA U3 (U3 snoRNA), harboring the atypical C/D boxes, is involved in 18S ribosomal RNA (18S rRNA) synthesis; however, the mechanism of U3 snoRNA in Pterygia remains unclear. Methods: Primary HCFs and HPFs were separated and cultured from fresh conjunctival grafts and Pterygia tissues. The PLKO.1 lentiviral system and CRISPR/Cas9 recombinant construct were, respectively, used to overexpress and silence U3 snoRNA in HPF and HCF cells for further specific phenotypes analysis. RNA-seq and TMT-labeled quantitative protein mass spectrometry were utilized to evaluate the effect of U3 snoRNA on mRNA transcripts and protein synthesis. Results: Reduced U3 snoRNA in Pterygia promotes HCF or HPF cells' proliferation, migration, and cell cycle but has no significant effect on apoptosis. U3 snoRNA modulates 18S rRNA synthesis through shearing precursor ribosomal RNA 47S rRNA at the 5′ external transcribed spacer (5′ ETS). Moreover, the altered U3 snoRNA causes mRNA and protein differential expression in HCF or HPF cells. Conclusion: The atypical U3 snoRNA regulates the translation of specific proteins to exert a suppressive function in Pterygia through modulating the 18S RNA synthesis. Here, we uncover a novel insight into U3 snoRNA biology in the development of Pterygia.

2022-05-20 | PXD030801 | Pride

Alterations of ribosomal RNA pseudouridylation in human breast cancer

Project description:RNA modifications are key regulatory factors for several biological and pathological processes. They are abundantly represented on ribosomal RNA (rRNA), where they contribute to regulate ribosomal function in mRNA translation. Altered RNA modification pathways have been linked to tumorigenesis as well as to other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern in rRNA in breast cancer samples exploiting the RBS-Seq technique involving RNA bisulfite treatment coupled with a new NGS approach. We found a wide variability among patients at different sites. The most dysregulated positions in tumors turned out to be hypermodified with respect to a reference RNA. As for 2’O-methylation level of rRNA modification, we detected variable and stable pseudouridine sites, with the most stable sites being the most evolutionary conserved. We also observed that pseudouridylation levels at specific sites are related to some clinical and bio-pathological tumor features and are able to distinguish different patient clusters. This study is the first example of the contribution that newly available high-throughput approaches for site specific pseudouridine detection can provide to the understanding of the intrinsic ribosomal changes occurring in human tumors.

2023-06-07 | GSE220967 | GEO

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