SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Su, Hexiu; Hu, Juncheng; Huang, Liang; Yang, Yang; Thenoz, Morgan; Kuchmiy, Anna; Hu, Yufeng; Li, Peng; Feng, Hui; Zhou, Yu; Taghon, Tom; Van Vlierberghe, Pieter; Qing, Guoliang; Chen, Zhichao; Liu, Hudan
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 15
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06523-4
• Languages: English
• ISSNs: 2041-1723

Abstract

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 theSHQ1 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 thatSHQ1 depletion impairs widespread RNA splicing, andMYC is one of the most prominently downregulated genes due to inefficient splicing.MYC overexpression significantly rescues T-ALL cell death resulted fromSHQ1 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 intoMYC regulation. T-acute lymphoblastic leukemia is an aggressive cancer. Here the authors provide insights into the functional role of SHQ1, an H/ACA snoRNP assembly factor involved in snRNA pseudouridylation, in T-lymphoblastic leukemia cell survival through regulating the maturation of MYC mRNA.