FUS modulates the level of ribosomal RNA modifications by regulating a subset of snoRNA expression [RiboMeth-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201972 | GEO | 2023/03/15
REPOSITORIES: GEO
Similar Datasets
Project description:FUS is a nucleocytoplasmic protein involved in many processes such as RNA transport, translation, and metabolism as well as genomic maintenance. FUS mutations are found in several neurodegenerative diseases. We find that FUS knockout (KO) affects the expression of many C/D box snoRNAs, H/ACA box snoRNAs and scaRNAs. snoRNAs notably serve as adaptors for the 2'-O-methylation (2'-O-me) and pseudouridylation of ribosomal RNA (rRNA). We show that knockout and FUS mutation alter the levels of 2'-O-Me and pseudouridylation at several rRNA sites.
2023-02-21 | GSE202524 | GEO
Project description:FUS is a nucleocytoplasmic protein involved in many processes such as RNA transport, translation, and metabolism as well as genomic maintenance. FUS mutations are found in several neurodegenerative diseases. We find that FUS knockout (KO) and FUS mutation affects the expression of many C/D box snoRNAs, H/ACA box snoRNAs and scaRNAs. snoRNAs notably serve as adaptors for the 2'-O-methylation (2'-O-me) and pseudouridylation of ribosomal RNA (rRNA).
2023-02-21 | GSE202529 | GEO
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
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 | GSE140618 | GEO
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 | GSE139812 | GEO
Project description:Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). There are two types of snoRNAs, box C/D, which typically guide 2’-O-methylation, and box H/ACA, which guide pseudouridylation. As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, the contributions of H/ACA box and C/D box snoRNAs to the biology of cancer cells remain unclear. To understand the contribution of snoRNAs to cancer progression and aggressiveness we examined their abundance patterns in high-grade serous ovarian carcinomas (HGSC) and serous borderline tumors (SBT), using a newly developed snoRNA sensitive sequencing technique. Surprisingly, the results indicate that while abundance of a selected group of H/ACA snoRNAs increases, most C/D snoRNAs remain stable or decrease in HGSC compared to SBT. This suggests that induction of ribosome biogenesis and translation in HGSC does not require a general increase in snoRNAs expression but depends upon the upregulation of a handful of key H/ACA snoRNAs. This subgroup accurately discriminates between SBT and HGSC underlining their potential as biomarkers of tumor aggressiveness. Remarkably, knockdown of HGSC associated H/ACA snoRNAs, but not their host genes, inhibits cell proliferation and induces apoptosis of model ovarian cancer cell lines. Together our data indicate that specific H/ACA snoRNAs promote tumor aggressiveness through the induction of cell proliferation and resistance to apoptosis.
2021-12-08 | GSE181496 | GEO
Project description:Background: In the experiment where we exposed chondrocytes of 4 healthy donors to OA-SF for 14 days we found several 2’O-methylation and pseudouridylation sites to be differentially modified in OA-SF condition compared to control (regular medium condition). We linked these PTMs to box C/D and H/ACA snoRNAs and selected 7 sites for validation. We did a CRISR/Cas9 mediated knock-down (KD) (not a complete knock-out (KO), as we didn’t pick clones) of these seven selected snoRNAs. Out of these seven snoRNAs, snoRNA33 knock-down stood out as the pseudouridylation at the corresposing site basically disappeared. We also saw differences in translation initiation and fidelity in snoRNA33 depleted cells. Therefore we decided to explore whether the ribosome composition (core and associated ribosomal proteins) is different in cells lacking snoRNA33 = RiboProteome samples (RP) and whether the proteome of these cells is different = Proteome samples (P). In both cases we used a GFP targeting CRISPR/Cas9 cell line as a control.
2023-10-24 | PXD042545 | Pride
Project description:Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs). scaRNAs are strongly downregulated when PARN and TOE1 are compromised together, leading to defects in small nuclear RNA (snRNA) pseudouridylation. They also function redundantly in the biogenesis of telomerase RNA component (TERC), which shares sequence motifs found in H/ACA box scaRNAs. Our findings extend the knowledge of nuclear ncRNA biogenesis, and they provide insights into the pathology of PARN/TOE1-associated genetic disorders whose therapeutic treatments are currently unavailable.
2018-03-30 | GSE111511 | GEO
Project description:Small nucleolar RNAs (snoRNAs) guide chemical modifications of ribosomal and small nuclear RNAs, functions that are carried out in the nucleus. While most snoRNAs reside in the nucleolus, a growing body of evidence indicates that snoRNAs are also present in the cytoplasm and that snoRNAs move between the nucleus and cytoplasm by a mechanism that is regulated by lipotoxic and oxidative stress. Here, in a genome-wide shRNA-based screen, we identified nuclear export factor 3 (NXF3) as a transporter that alters the nucleocytoplasmic distribution of box C/D snoRNAs from the ribosomal protein L13a (Rpl13a) locus. Using RNA-sequencing analysis, we show that NXF3 associates not only with Rpl13a snoRNAs, but also with a broad range of box C/D and box H/ACA snoRNAs. Under homeostatic conditions, gain or loss of function of NXF3, but not related family member NXF1, decreases or increases cytosolic Rpl13a snoRNAs, respectively. Furthermore, treatment with the adenylyl cyclase activator forskolin diminishes cytosolic localization of the Rpl13a snoRNAs through a mechanism that is dependent on NXF3, but not NXF1. Our results provide evidence of a new role for NXF3 in regulating the distribution of snoRNAs between the nuclear and cytoplasmic compartments.
2017-10-30 | GSE106301 | GEO
Project description:Pseudo-seq was used to measure differences in the extent of pseudouridine (Ψ) modification in rRNA from mice haploinsufficient for the H/ACA biogenesis factor Naf1 compared to wild- type. We measured telomerase RNA levels as well as a sample of box H/ACA RNAs and found they were all decreased in Naf1+/- mice. Nevertheless, Naf1+/- mice had minimally decreased levels of pseudouridylation at the rRNA sites queried. This was not associated with any phenotypic abnormalities in vivo in these mice which we examined for hematopoeitic, liver, testes and brain defects. CMC treatment of RNA followed by next generation sequencing was used to measure the extent of pseudouridylation at mapped mouse rRNA Ψ sites.
2016-08-07 | E-GEOD-78063 | biostudies-arrayexpress