The splicing factor RBM25 controls MYC activity in acute myeloid leukemia

Research output: Contribution to journal › Journal article › Research › peer-review

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The splicing factor RBM25 controls MYC activity in acute myeloid leukemia. / Ge, Ying; Schuster, Mikkel Bruhn; Pundhir, Sachin; Rapin, Nicolas; Bagger, Frederik Otzen; Sidiropoulos, Nikos; Hashem, Nadia; Porse, Bo Torben.

In: Nature Communications, Vol. 10, No. 1, 172, 2019, p. 1-14.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ge, Y, Schuster, MB, Pundhir, S, Rapin, N, Bagger, FO, Sidiropoulos, N, Hashem, N & Porse, BT 2019, 'The splicing factor RBM25 controls MYC activity in acute myeloid leukemia', Nature Communications, vol. 10, no. 1, 172, pp. 1-14. https://doi.org/10.1038/s41467-018-08076-y

APA

Ge, Y., Schuster, M. B., Pundhir, S., Rapin, N., Bagger, F. O., Sidiropoulos, N., Hashem, N., & Porse, B. T. (2019). The splicing factor RBM25 controls MYC activity in acute myeloid leukemia. Nature Communications, 10(1), 1-14. [172]. https://doi.org/10.1038/s41467-018-08076-y

Vancouver

Ge Y, Schuster MB, Pundhir S, Rapin N, Bagger FO, Sidiropoulos N et al. The splicing factor RBM25 controls MYC activity in acute myeloid leukemia. Nature Communications. 2019;10(1):1-14. 172. https://doi.org/10.1038/s41467-018-08076-y

Author

Ge, Ying ; Schuster, Mikkel Bruhn ; Pundhir, Sachin ; Rapin, Nicolas ; Bagger, Frederik Otzen ; Sidiropoulos, Nikos ; Hashem, Nadia ; Porse, Bo Torben. / The splicing factor RBM25 controls MYC activity in acute myeloid leukemia. In: Nature Communications. 2019 ; Vol. 10, No. 1. pp. 1-14.

Bibtex

@article{451223046cc14cd187c454c77180c326,
title = "The splicing factor RBM25 controls MYC activity in acute myeloid leukemia",
abstract = "Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in acute myeloid leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that {"}non-mutated{"} splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This has led to the identification of the splicing regulator RBM25 as a novel tumor suppressor. In multiple human leukemic cell lines, knockdown of RBM25 promotes proliferation and decreases apoptosis. Mechanistically, we show that RBM25 controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1. This mechanism is also operative in human AML patients where low RBM25 levels are associated with high MYC activity and poor outcome. Thus, we demonstrate that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels.",
author = "Ying Ge and Schuster, {Mikkel Bruhn} and Sachin Pundhir and Nicolas Rapin and Bagger, {Frederik Otzen} and Nikos Sidiropoulos and Nadia Hashem and Porse, {Bo Torben}",
year = "2019",
doi = "10.1038/s41467-018-08076-y",
language = "English",
volume = "10",
pages = "1--14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - The splicing factor RBM25 controls MYC activity in acute myeloid leukemia

AU - Ge, Ying

AU - Schuster, Mikkel Bruhn

AU - Pundhir, Sachin

AU - Rapin, Nicolas

AU - Bagger, Frederik Otzen

AU - Sidiropoulos, Nikos

AU - Hashem, Nadia

AU - Porse, Bo Torben

PY - 2019

Y1 - 2019

N2 - Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in acute myeloid leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that "non-mutated" splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This has led to the identification of the splicing regulator RBM25 as a novel tumor suppressor. In multiple human leukemic cell lines, knockdown of RBM25 promotes proliferation and decreases apoptosis. Mechanistically, we show that RBM25 controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1. This mechanism is also operative in human AML patients where low RBM25 levels are associated with high MYC activity and poor outcome. Thus, we demonstrate that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels.

AB - Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in acute myeloid leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that "non-mutated" splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This has led to the identification of the splicing regulator RBM25 as a novel tumor suppressor. In multiple human leukemic cell lines, knockdown of RBM25 promotes proliferation and decreases apoptosis. Mechanistically, we show that RBM25 controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1. This mechanism is also operative in human AML patients where low RBM25 levels are associated with high MYC activity and poor outcome. Thus, we demonstrate that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels.

U2 - 10.1038/s41467-018-08076-y

DO - 10.1038/s41467-018-08076-y

M3 - Journal article

C2 - 30635567

VL - 10

SP - 1

EP - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 172

ER -

ID: 211854806