Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FuHsi initiates the nucleolus biogenesis and regulates mouse development.

ABSTRACT: The nucleolus is a membraneless condensate in eukaryotic cell nucleus, which is composed of three layers of fibrillar center (FC), dense fibrillar component (DFC), as well as granular component (GC) and regulates ribosome biogenesis1,2. The first step in nucleolar biogenesis is transcription of ribosomal DNA (rDNA) genes, termed as nucleolar organizer regions (NORs), which is binding by upstream binding factor (UBF) and other transcription-associated proteins3-6. However, whether any molecule early onset of rDNA is involved in nucleolar biogenesis remains unknown. Here, we analyze the candidate long noncoding RNAs (lncRNAs) encoded microproteins, preferentially as proteins, based on the nucleoli mass spectrometry (MS) data and identify 7 potential proteins that may be enriched in the nucleolus. Among these proteins, FuHsi solely builds a site that subsequently recruits rDNA, UBF and other transcription-associated proteins to initiate the nucleolus biogenesis. Functionally, FuHsi depletion leads to a dissolved nucleolus, as indicated by the disappearance of rDNA, FC, DFC and GC. Deficient FuHsi impairs rDNA transcription and subsequent ribosome biogenesis. Furthermore, Fuhsi is an evolutionarily conserved protein in mouse, and homolog protein can functionally replace each other in vitro. The heterozygous Fuhsi knockout (KO) mice die within four weeks, and exhibit small size as well as decreased weight, in concordance with the decreased ribosome biogenesis, who are rescued by transgenic human FuHsi. This study reveals that FuHsi is a core protein that initiates nucleolar biogenesis and regulates mouse development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253977 | GEO | 2024/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

URB1 ensures 3' end processing of pre-rRNAs to prevent exosome-dependent degradation and is required for development [SHAPE-MaP]

Project description:The nucleolus composes hundreds of proteins that play distinct roles in ribosomal RNA (rRNA) processing within Fibrillar Center/Dense Fibrillar Component (FC/DFC) units and ribosome assembly in Granular Component (GC). The sub-nucleolar localization of most proteins and how their unique localization facilitates rRNA processing have remained elusive. By screening 200 nucleolar candidate proteins with high-resolution, live-cell microscopy, we identified a previously undescribed sub-nucleolar compartment, named the periphery of DFC (PDFC). Among the 12 proteins identified in PDFC, URB1 (unhealthy ribosome biogenesis 1) is required for PDFC organization and proper 3' end processing of 47S pre-rRNA. URB1 binds between the 28S rRNA and the 3' external transcribed spacer (3' ETS) to ensure 3' ETS removal, which occurs at the DFC/PDFC boundary. Loss of URB1 leads to accumulation of aberrant 3' ETS-retained 32S pre-rRNA variants, which activates exosome-dependent nucleolar surveillance. This causes decreased 28S rRNA production, reduced cell proliferation and retarded mouse embryonic pre-implementation development. Furthermore, urb1 depletion results in developmental craniofacial disorder in zebrafish, which can be at least partially rescued by further depleting exosome components. Together, this study provides new insights into functional sub-nucleolar organizations, identifies a physiologically essential step in rRNA maturation and emphasizes the exosome-dependent pre-rRNA surveillance pathway.

2023-01-04 | GSE196625 | GEO

URB1 ensures 3' end processing of pre-rRNAs to prevent exosome-dependent degradation and is required for development

2023-01-04 | GSE194413 | GEO

Activation of PARP-1 by snoRNAs Controls Ribosome Biogenesis and Cell Growth via the RNA Helicase DDX21 (RNA-Seq)

Project description:PARP inhibitors (PARPi) prevent cancer cell growth by inducing synthetic lethality with DNA repair defects (e.g., in BRCA1/2 mutant cells). We have identified an alternate pathway for PARPi-mediated growth control in BRCA1/2-intact breast cancer cells involving rDNA transcription and ribosome biogenesis. PARP-1 binds to snoRNAs, which stimulate PARP-1 catalytic activity in the nucleolus independent of DNA damage. Activated PARP-1 ADP-ribosylates DDX21, an RNA helicase that localizes to nucleoli and promotes rDNA transcription when ADP-ribosylated. Treatment with PARPi or mutation of the ADP-ribosylation sites reduce DDX21 nucleolar localization, rDNA transcription, ribosome biogenesis, protein translation, and cell growth. The salient features of this pathway are evident in xenografts in mice and human breast cancer patient samples. Elevated levels of PARP-1 and nucleolar DDX21 are associated with cancer-related outcomes. Our studies provide a mechanistic rationale for efficacy of PARPi in cancer cells lacking defects in DNA repair whose growth is inhibited by PARPi.

2019-07-31 | GSE115760 | GEO

Ribosome biogenesis disruption mediated chromatin structure changes in C. elegans larvae revealed by SRAtac, an integrated, customizable end to end analysis pipeline for ATAC-seq

Project description:Nucleolus is the largest nuclear body and the site of ribosome biogenesis. Recent studies implicated an important role for nucleolus as an organizer of chromatin architecture. However, lack of genetic tools to disrupt nucleolar ribosome biogenesis limited our understanding of the causal link between chromatin architecture and nucleolar ribosome assembly. Here, we introduce SRAlign, a reproducible, configurable, and extensible NGS data processing workflow as well as SRAtac, a customizable and end to end analysis pipeline for ATAC-seq analysis. We apply these methods to determine the changes in chromatin accessibility upon specific depletion of an RNA polymerase I subunit, RPOA-2, a ribosome biogenesis components RRB-1 in Caenorhabditis elegans. We found highly comparable changes in chromatin accessibility in response to these two perturbations. However, the identified chromatin accessibility changes are weakly correlated with gene expression changes. Our results support feedback from nucleolar ribosome biogenesis to chromatin structure during the L1 stage in C. elegans but question the significance of these changes on gene expression.

2022-11-29 | GSE218280 | GEO

Functional analysis of HD2C in Arabidopsis

Project description:Ribosome biogenesis is a fundamental process required for all cellular activities. Histone deacetylases play critical roles in many biological processes including transcriptional repression and rDNA silencing. However, their function in pre-rRNA processing remains poorly understood. Here, we discovered a previously uncharacterized role of Arabidopsis histone deacetylase HD2C in pre-rRNA processing via both canonical and non-canonical manners. HD2C interacts with HD2B and forms homo- and/or hetero-oligomers in the nucleolus. Depletion of HD2C and HD2B induces a ribosome biogenesis deficiency morphological phenotype and aberrant accumulation of 18S pre-rRNA intermediates. Our genome-wide analysis revealed that HD2C binds and represses the expression of key genes involved in ribosome biogenesis. Using RNA immunoprecipitation and sequencing, we further uncovered a non-canonical mechanism of HD2C directly associating with pre-rRNA and small nucleolar RNAs to regulate rRNA methylation. Together, this study reveals a multifaceted role of HD2C in ribosome biogenesis and provides mechanistic insights into how histone deacetylases modulate rRNA maturation at both transcriptional and post-transcriptional levels.

2018-03-01 | GSE107883 | GEO

rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin [RNA-seq]

Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.

2021-09-15 | GSE166025 | GEO