دورية أكاديمية
SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival
| العنوان: | SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival |
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| المؤلفون: | Su, Hexiu, Hu, Juncheng, Huang, Liang, Yang, Yang, Thénoz, Morgan, Kuchmiy, Anna, Hu, Yufeng, Li, Peng, Feng, Hui, Zhou, Yu, Taghon, Tom, Van Vlierberghe, Pieter, Qing, Guoliang, Chen, Zhichao, Liu, Hudan |
| المصدر: | NATURE COMMUNICATIONS ; ISSN: 2041-1723 |
| سنة النشر: | 2018 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, Biology and Life Sciences, H/ACA SMALL NUCLEOLAR, TUMOR-SUPPRESSOR, C-MYC, GENE-EXPRESSION, CANCER, NOTCH1, PSEUDOURIDYLATION, TARGET, LEUKEMOGENESIS, SENSITIVITY |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/8613044Test; http://hdl.handle.net/1854/LU-8613044Test; http://dx.doi.org/10.1038/s41467-018-06523-4Test; https://biblio.ugent.be/publication/8613044/file/8613056Test |
| DOI: | 10.1038/s41467-018-06523-4 |
| الإتاحة: | https://doi.org/10.1038/s41467-018-06523-4Test https://biblio.ugent.be/publication/8613044Test http://hdl.handle.net/1854/LU-8613044Test https://biblio.ugent.be/publication/8613044/file/8613056Test |
| حقوق: | Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.F9047A19 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-018-06523-4 |
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