Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells through alternative splicing of c-Mpl

Xiao, Nan; Laha, Suparna; Das, Shankar; Morlock, Kayla; Jesneck, Jonathan L.; Raffel, Glen D.

doi:10.1182/blood-2014-08-593392

Cited by 40 publications

(42 citation statements)

References 43 publications

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“… 25 In RBM15 knockout mouse, it showed that RBM15 played an essential role in developing of a variety of tissues, especially in the maintenance of long-term hematopoietic stem cell homeostasis and the differentiation of megakaryon and B cells. 26 , 27 In addition, it also contributed to chromosomal translocation in acute megakaryocytic leukemia. 28 However, so far, there have been no reports on the mechanism of RBM15 involvement in the malignant phenotype of GC.…”

Section: Discussionmentioning

confidence: 99%

<p>To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer</p>

Zhang

Piao

Wang

et al. 2020

OTT

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Background Gastric cancer (GC) accounts for high mortality. RNA methylation has recently gained interest as markers in specific tumors. This study aimed to uncover the function of the roles of 25 RNA methylation regulators in GC. Methods RNA sequence and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. “STRING” and R were performed to analyze the correlation among the methylase. COX and LASSO were performed to screen for prognostic associated RNA methylation regulators. A prognostic model was established based on the expression of methylase. RT-PCR and immunohistochemistry detected the expression of methylase in GC cells and tissue. Kaplan–Meier curve and Cox analysis were applied to evaluate the effectiveness of the model. Results The prediction model was established based on the expression of m6A RNA methylation regulators FTO (fat mass and obesity-associated) and RBM15 (RNA binding motif protein 15). Based on the model, GC patients were divided into “high risk” and “low risk” groups to compare the differences in survival. The model was re-evaluated with the clinical data of our center. Conclusion The two-methylase combination model was an independent prognostic factor of GC.

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Section: Discussionmentioning

confidence: 99%

<p>To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer</p>

Zhang

Piao

Wang

et al. 2020

OTT

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“…regulators include KAT2B, HDAC1/2, SWI/SNF, CTCF, MeCP2, WDR5/MLL (an H3K4 methyltransferase), EZH2 (a repressor), and mediator , Sjolinder et al, 2005, Tyagi et al, 2009, Khan et al, 2012, Maxwell et al, 2013, Tsai et al, 2010, Gardini and Shiekhattar, 2015. SETD1B binds to the MPL transcript (Xiao et al, 2014). Thus, there is evidence that the enzymes catalyzing H3K4 trimethylation are associated with RNA.…”

Section: H3k4me3 Readersmentioning

confidence: 96%

“…The human MPL gene codes for a type 1 hematopoietic cytokine receptor as well a truncated protein when the transcript is alternatively spliced at exons 9 and 10 (Xiao et al, 2014). The…”

Section: Page 5 Of 40mentioning

confidence: 99%

Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing

Davie

Delcuve

2016

Biochem. Cell Biol.

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Histone H3 lysine 4 trimethylation (H3K4me3) is often stated as a mark of transcriptionally active promoters. However, closer study of the positioning of H3K4me3 shows the mark locating primarily after the first exon at the 5' splice site and overlapping with a CpG island in mammalian cells. There are several enzyme complexes that are involved in the placement of the H3K4me3 mark, including multiple protein complexes containing SETD1A, SETD1B, and MLL1 enzymes (writers). CXXC1, which is associated with SETD1A and SETD1B, target these enzymes to unmethylated CpG islands. Lysine demethylases (KDM5 family members, erasers) demethylate H3K4me3. The H3K4me3 mark is recognized by several proteins (readers), including lysine acetyltransferase complexes, chromatin remodelers, and RNA bound proteins involved in pre-mRNA splicing. Interestingly, attenuation of H3K4me3 impacts pre-mRNA splicing, and inhibition of pre-mRNA splicing attenuates H3K4me3.

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“…Previous data has demonstrated that protein arginine methyltransferase 1 (PRMT1) has high expression in leukemia, particularly in M7 (5). RNA binding motif protein 15 (RBM15) is required for the long-term maintenance of the homeostasis of hematopoietic stem cells and for MK differentiation (6,7). RBM15 stability is controlled by PRMT1 via CNOT4-mediated ubiquitylation (8).…”

Section: Introductionmentioning

confidence: 99%

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

Jin

Song

et al. 2018

Exp Ther Med

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Abstract. Protein arginine methyltransferase 1 (PRMT1) serves pivotal roles in various cellular processes. However, its role in megakaryocytic differentiation has not been clearly reported. The aim of the present study was to explore the role of the PRMT-RNA binding motif protein 15 (RBM15) axis in human MK differentiation and the feasibility of targeting PRMT1 for leukemia treatment. In the present study, PRMT1 was overexpressed and the RBM15 protein was knocked down in human umbilical cord blood cluster of differentiation (CD)34 + cells and the cells were then cultured in megakaryocytic differentiation medium. Flow cytometry was used to analyze CD41 and CD42 double-positive cells, as well as the protein expression levels of PRMT1 and RBM15. The results demonstrated that human cord blood CD34 + cells differentiate into mature MKs in high thrombopoitin medium, as demonstrated by CD41 and CD42 expression. Overexpression of PRMT1 in human umbilical cord blood CD34 + cells blocked the maturation of megakaryocytic cells. Knockdown of RBM15 by short hairpin RNA produced less mature MKs. PRMT1 inhibitor rescued PRMT1-blocked megakaryocytic differentiation. These results provide evidence for a novel role of PRMT1 in the negative regulation of megakaryocytic differentiation. PRMT1 may be a therapeutic target for leukemia treatment.

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Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells through alternative splicing of c-Mpl

Cited by 40 publications

References 43 publications

<p>To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer</p>

<p>To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer</p>

Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

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