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Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

ABSTRACT: Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

PROVIDER: PRJNA673704 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12960923.fastq.gz	Fastqsanger.gz
	SRR12960924.fastq.gz	Fastqsanger.gz
	SRR12960925.fastq.gz	Fastqsanger.gz
	SRR12960926.fastq.gz	Fastqsanger.gz
	SRR12960927.fastq.gz	Fastqsanger.gz

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Similar Datasets

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

Project description:Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

| PRJNA673701 | ENA

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

Project description:Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Yet, information on physiological roles and underlying signaling mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with a novel multiple congenital anomaly disorder caused by hemizygous variants in OTUD5, encoding a K48-/K63-linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of a select group of chromatin regulators. These include ARID1A/B, HDAC2, and HCF1, mutation of which underlie different developmental disorders that exhibit phenotypic overlap with OTUD5 patients. Consequently, loss of OTUD5 during early differentiation leads to less accessible chromatin at neuroectodermal enhancers and thus aberrant rewiring of gene expression networks. Our study describes a novel developmental disorder we name LINKED (LINKage-specific-deubiquitylation-deficiency-induced Embryonic Defects) syndrome, provides a previously unrecognized mechanistic link between phenotypically related diseases, and reveals linkage-specific ubiquitin cleavage from substrate groups (i.e. chromatin remodelers) as an essential mode of signaling required to coordinate embryonic differentiation pathways.

2020-11-02 | GSE160589 | GEO

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

2020-11-02 | GSE160588 | GEO

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

Project description:Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

| PRJNA673703 | ENA

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation.

Project description:Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with multiple congenital anomalies caused by hemizygous variants in OTUD5, encoding a K48/K63 linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of select chromatin regulators (e.g., ARID1A/B, histone deacetylase 2, and HCF1), mutations of which underlie diseases that exhibit phenotypic overlap with OTUD5 patients. Loss of OTUD5 during differentiation leads to less accessible chromatin at neuroectodermal enhancers and aberrant gene expression. Our study describes a previously unidentified disorder we name LINKED (LINKage-specific deubiquitylation deficiency-induced Embryonic Defects) syndrome and reveals linkage-specific ubiquitin cleavage from chromatin remodelers as an essential signaling mode that coordinates chromatin remodeling during embryogenesis.

| S-EPMC7817106 | biostudies-literature

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

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

2020-11-02 | GSE160590 | GEO

A combinatorial ubiquitin code degrades substrates protected by deubiquitylation

Project description:Reversibility of protein ubiquitylation play essential roles in cellular protein homeostasis. How substrates stabilized by deubiquitylation are directed for degradation remains largely elusive. Here, we show that the branched ubiquitin chains promote the degradation of the deubiquitylase (DUB) OTUD5. OTUD5 is sequentially modified by TRIP12 and UBR5, E3s specific for the K29 and K48 linkages, respectively, resulting in the conjugation of K29/K48 branched ubiquitin chains. The TRIP12-OTUD5 antagonism regulates TNF--induced NF-B signaling. Mechanistically, while OTUD5 readily cleaves K48-linkages, K29-linkages are resistant against OTUD5 activity. Consequently, K29-linkages overcome OTUD5 DUB activity to facilitate UBR5-dependent K48-linked chain branching. Regarding generality, this mechanism adopts to other TRIP12 substrates associated with OTUD5. These results uncover a cellular unique strategy in which the sequential addition of DUB-resistant and proteasome-targeting ubiquitin linkages efficiently promote degradation of substrates protected by deubiquitylation, underscoring the role of branched ubiquitin chains in the quality control of hard-to-degrade substrates.

2025-02-19 | GSE273273 | GEO

Whole-transcriptome analysis using RNA sequencing in OTUD5-wild type, OTUD5-null, and GDC0349-treated HEK293 cells

Project description:Whole-transcriptome analysis was performed on RNA from OTUD5-wild type, OTUD5-null, and GDC0349-treated HEK293 cells to identify the cellular processes regulated by OTUD5 and mTOR simultaneously.

2021-03-18 | GSE135078 | GEO

OTUD5 complex mass spectrometry

Project description:DUBs are involved in various pathways and signalling networks by pairing with E3 ubiquitin ligases in protein complexes. In order to test whether OTUD5 associates with an E3 ubiquitin ligase to regulate cell proliferation, the stable Flag-OTUD5/Hep3B cell line was established by transfecting Hep3B cells with plasmids expressing pCIN4-Flag-OTUD5. The cellular factors interacting with OTUD5 were purified by anti-Flag antibody-conjugated M2 beads.

2020-09-11 | PXD019907 | Pride

Ubiquitination analysis of OTUD5

Project description:TMT quantification of UBR5 knockdown HT1080 cells. Label-free quantification of OTUD5-interacting proteins.

2025-02-20 | PXD054556 | Pride