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These data provide a catalog of copy-number associated gene dependencies and identify partial copy-loss of wild-type SF3B1 (zeige SF3B2 Proteine) as a novel, non-driver cancer gene dependency.
although blocking the function of SF3b elicits a massive accumulation of unspliced pre-mRNAs in the nucleus, intron-containing transcripts can still bind the ALYREF (zeige THOC4 Proteine) export factor and be transported to the cytoplasm, where they trigger an alternative nonsense-mediated decay pathway.
this study shows that DNMT3A (zeige DNMT3A Proteine) mutations are present in a significant proportion of SF3B1mut patients with RARS (zeige RARS Proteine) and its presence has a clearly negative impact on outcomes, determining a higher RBC (zeige CACNA1C Proteine) transfusion dependency, higher risk of progression to AML (zeige RUNX1 Proteine), and lower OS.
Somatic SF3B1 mutations are associated with metastatic NUT midline carcinoma.
Fanconi anemia (zeige PALB2 Proteine) FANCD2 and FANCI (zeige FANCI Proteine) proteins regulate the nuclear dynamics of splicing factors, such as SF3B1 (zeige SF3B2 Proteine).
The frequently mutated SF3B1 (zeige SF3B2 Proteine) residues contact the pre-mRNA splice site. Based on structural homology with other spliceosome subunits, and recent findings of altered RNA binding by mutant U2AF1 (zeige U2AF1 Proteine) proteins, we suggest that affected U2AF1 (zeige U2AF1 Proteine) residues also contact pre-mRNA.
The aberrantly spliced target genes and deregulated cellular pathways associated with the commonly mutated splicing factor (zeige SLU7 Proteine) genes in myelodysplastic syndromes (SF3B1 (zeige SF3B2 Proteine), SRSF2 (zeige SRSF2 Proteine) and U2AF1 (zeige U2AF1 Proteine)) are being identified, illuminating the molecular mechanisms underlying the disease. (Review)
These findings provide evidence of a multipotent lymphomyeloid Hematopoietic stem cell origin of SF3B1 (zeige SF3B2 Proteine) mutations in myelodysplastic syndrome with ring sideroblasts patients.
Mutation in SF3B1 (zeige SF3B2 Proteine) gene is associated with Uveal Melanoma.
Mutation in SF3B1 (zeige SF3B2 Proteine) is associated with myelodysplastic syndrome and chronic lymphocytic leukemia.
Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse.
Sf3b1(K700E) mice develop macrocytic anemia (zeige TCN2 Proteine) due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC (zeige FUT1 Proteine)) expansion.
myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1alpha (HIF1alpha (zeige HIF1A Proteine)) activation of SF3B1 and SF3B1-mediated splice switching of KHK (zeige KHK Proteine)-A to KHK (zeige KHK Proteine)-C
Sf3b1 isrequired for the blastocyst formation.
SF3B1 plays an important role in the regulation of hematopoietic stem cells, whereas SF3B1 haploinsufficiency itself is not associated with the myelodysplastic syndrome phenotype with ring sideroblasts.
The level of Sf3b1 expression is critical for the proliferative capacity of hematopoietic stem cells. Depletion of Sf3b1 impairs proliferative capacity of hematopoietic stem cells but is not sufficient to induce myelodysplasia.
SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes.
the active spliceosome, containing SAP155 phosphorylated by DYRKIA, performs pre-mRNA splicing in spermatogonia during testicular development
active spliceosome, containing phosphorylated SAP155, performs pre-mRNA splicing on chromatin concomitant with transcription during testicular development.
Sf3b1 and Polycomb (zeige CBX2 Proteine) group (PcG) proteins interaction is essential for true PcG-mediated repression of Hox (zeige MSH2 Proteine) genes.
Data indicate that splicing factor 3b (zeige SF3B14 Proteine), subunit 1 (sf3b1) mutation causes aberrant splicing of sf3b1 resulting in functional and predicted non-functional transcripts and a 90% reduction in full-length Sf3b1 protein.
This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms.
, pre-mRNA processing 10
, pre-mRNA splicing factor SF3b, 155 kDa subunit
, spliceosome-associated protein 155
, splicing factor 3B subunit 1
, pre-mRNA-splicing factor SF3b 155 kDa subunit
, splicing factor 3b, subunit 1, 155 kDa
, transforming growth factor alpha regulated gene 4
, 146 kDa nuclear protein
, splicing factor 3b, subunit 1, 155kDa
, splicing factor 3B subunit 1-like
, splicing factor 3b, subunit 1, 155kD