Screening of <scp>JAK</scp>2 V617F and MPL W515 K/L negative essential thrombocythaemia patients for mutations in <scp>SESN</scp>2, <scp>DNAJC</scp>17, <scp>ST</scp>13, <scp>TOP</scp>1<scp>MT</scp>, and <scp>NTRK</scp>1

Assaf, Carla Al; Lierman, Els; Devos, Timothy; Billiet, Johan; Graux, Carlos; Papadopoulos, Petros; Vandenberghe, Peter

doi:10.1111/bjh.12790

Cited by 4 publications

(4 citation statements)

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“…Thus, further studies are required to establish whether DNAJC17 plays a role in general or specific alternative splicing events. Nevertheless, its involvement in such a crucial phenomenon should hypothetically explain the embryo lethality in DNAJC17 knockout mouse as well as the association of different mutations in Dnajc17 to different complex disorders in humans 4 , 5 , 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Patel and collaborators identified homozygous truncating mutation that segregated in a family with an apparently novel syndrome of retinitis pigmentosa and hypogammaglobulinemia, thus highlighting Dnajc17 as a candidate gene for retinal dystrophy 4 . Two different missense mutations in exon 11 of the human DnaJc17 gene were identified in patients with essential thrombocythaemia by two independent studies 5 , 6 . Furthermore, DnaJc17 transcripts were found to be subjected to differential alternative splicing in blood cells from Autism Spectrum Disorder (ASD) 7 .…”

Section: Introductionmentioning

confidence: 99%

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DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components

Pascarella

Ferrandino

Credendino

et al. 2018

Sci Rep

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DNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse embryos die prior to implantation. In humans, germline homozygous mutations in DNAJC17 have been found in syndromic retinal dystrophy patients, while heterozygous mutations represent candidate pathogenic events for myeloproliferative disorders. Despite widespread expression and involvement in human diseases, DNAJC17 function is still poorly understood. Herein, we have investigated its function through high-throughput transcriptomic and proteomic approaches. DNAJC17-depleted cells transcriptome highlighted genes involved in general functional categories, mainly related to gene expression. Conversely, DNAJC17 interactome can be classified in very specific functional networks, with the most enriched one including proteins involved in splicing. Furthermore, several splicing-related interactors, were independently validated by co-immunoprecipitation and in vivo co-localization. Accordingly, co-localization of DNAJC17 with SC35, a marker of nuclear speckles, further supported its interaction with spliceosomal components. Lastly, DNAJC17 up-regulation enhanced splicing efficiency of minigene reporter in live cells, while its knockdown induced perturbations of splicing efficiency at whole genome level, as demonstrated by specific analysis of RNAseq data. In conclusion, our study strongly suggests a role of DNAJC17 in splicing-related processes and provides support to its recognized essential function in early development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components

Pascarella

Ferrandino

Credendino

et al. 2018

Sci Rep

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“…Mutations in the DNAJC17 gene have been reported to be associated with retinitis pigmentosa and hypogammaglobulinemia [ 34 ]. A mutation in the DNAJC17 gene has also been described in patients with essential thrombocytopenia [ 35 ]. To the best of our knowledge, our study is the first to describe an association between aflibercept intervention and DNAJC17.…”

Section: Discussionmentioning

confidence: 99%

Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17

Cehofski

Kruse

Alsing

et al. 2021

Journal of Ophthalmology

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Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF) used to treat macular edema following branch retinal vein occlusion (BRVO). Despite well-documented efficacy, there is limited knowledge about proteome changes following aflibercept intervention in BRVO. Proteome changes may provide insights into mechanisms of action as well as aspects related to safety profile. In seven Danish Landrace pigs, BRVO was induced with a well-established experimental model of argon laser-induced BRVO. BRVO was induced in both eyes. Three days after the induced BRVO, aflibercept was injected intravitreally in the right eyes, while the left eyes received intravitreal isotonic saline water. Retinas were collected 15 days after the induced BRVO and analyzed with label-free quantification liquid chromatography tandem mass spectrometry (LFQ LC-MS/MS). Fourteen proteins were changed in expression following aflibercept intervention in the BRVO model. LFQ LC-MS/MS identified an upregulation of DnaJ homolog subfamily C member 17 (DNAJC17) (fold change = 6.19) and a modest downregulation of isoform 2 of the protein encoded by N-myc downstream regulated gene 2 (NDRG2) (fold change = 0.40). NDRG2 was unchanged by Western blotting. In the additional significantly regulated proteins, only discrete changes were observed (fold changes 0.52–1.59). Our study is the first to report an association between aflibercept intervention and the heat shock protein DNAJC17. Our results indicate that the role of heat shock proteins in the treatment of BRVO should be further explored.

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“…Cwf23, the Cwc23 ortholog in S. pombe has a C-terminal RRM capable of binding RNA in vitro (Raut et al, 2019). Although the in vivo roles of Cwf23 orthologs and their contribution to the process of splicing are still unknown, mutations in DnaJC17, the human ortholog of Cwc23, have been linked to various human disorders including retinal dystrophy, thrombocythemia, congenital hypothyroidism with thyroid dysgenesis and Autism Spectrum Disorder (ASD) (AL Assaf et al, 2014; Hou et al, 2012; Patel et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Inclusion of Hsp70 co-chaperone and RNA binding activities facilitate optimal function of spliceosomal disassembly factor Cwf23 in intron-richSchizosaccharomyces pombe

Yadav,

Raut,

Roy

et al. 2024

Preprint

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Cwc23 is an essential J-domain protein that collaborates with the disassembly factor Ntr1 to facilitate spliceosomal disassembly. Although Cwc23 orthologs have been identified in spliceosomal extracts of many eukaryotes, their functionality in intron-rich eukaryotes remains largely unexplored. Here, we investigate the functionality of Cwf23, an ortholog of Cwc23 inSchizosaccharomyces pombe. Our study reveals that while the interaction between Cwf23 andSpNtr1 is conserved, it is not essential inS. pombe. Additionally, the RNA recognition motif (RRM) in Cwf23 is crucial for its function, as mutations in the RRM affect both growth and pre-mRNA splicing. Unlike its budding yeast counterpart, the J-domain of Cwf23 is indispensable, as J-domain mutants cannot support cell viability. These findings suggest a new paradigm in which the presence of a functional RRM and the essential nature of the J-domain underscore the increased requirements for an RNA-binding Hsp70 co-chaperone machinery in spliceosomal remodelling in “intron-rich” eukaryotes.

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Screening of JAK2 V617F and MPL W515 K/L negative essential thrombocythaemia patients for mutations in SESN2, DNAJC17, ST13, TOP1MT, and NTRK1

Cited by 4 publications

References 10 publications

DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components

DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components

Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17

Inclusion of Hsp70 co-chaperone and RNA binding activities facilitate optimal function of spliceosomal disassembly factor Cwf23 in intron-richSchizosaccharomyces pombe

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