澳门银河3980yh
20181015 SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival.
發布時間:2018-10-15  來源:  閱讀次數:
2018 Oct 15;9(1):4281. doi: 10.1038/s41467-018-06523-4.

SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival.

1, 2, 2, 3, 4, 5, 6, 7, 8, 9, 4, 6, 5, 2, 7, 10, 11, 12.

Abstract

T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with complicated heterogeneity. Although expression profiling reveals common elevated genes in distinct T-ALL subtypes, little is known about their functional role(s) and regulatory mechanism(s). We here show that SHQ1, an H/ACA snoRNP assembly factor involved in snRNA pseudouridylation, is highly expressed in T-ALL. Mechanistically, oncogenic NOTCH1 directly binds to the SHQ1 promoter and activates its transcription. SHQ1 depletion induces T-ALL cell death in vitro and prolongs animal survival in murine T-ALL models. RNA-Seq reveals that SHQ1 depletion impairs widespread RNA splicing, and MYC is one of the most prominently downregulated genes due to inefficient splicing. MYC overexpression significantly rescues T-ALL cell death resulted from SHQ1 inactivation. We herein report a mechanism of NOTCH1-SHQ1-MYC axis in T-cell leukemogenesis. These findings not only shed light on the role of SHQ1 in RNA splicing and tumorigenesis, but also provide additional insight into MYC regulation.


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