Chinese scientists have discovered a new mechanism of pathogenesis of acute T lymphocytic leukemia
Chinese scientists have discovered a new mechanism of pathogenesis of acute T lymphocytic leukemia
November 13, 2018 Source: Ministry of Science and Technology
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];On October 15th, the research team of Liu Hudan of Wuhan University Medical Research Institute and Chen Zhichao of the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology jointly published a paper on leukemia research in Nature Communications. This study demonstrates the functional and molecular mechanisms by which SHQ1 mediates the development of pseudo-lymphocyte leukemia (T-ALL) by mediating the pseudo-uracil modification of splicing RNA (U2 spliceosomal RNA), regulating pre-mRNA splicing.
In recent years, high frequency mutations in splicing-related genes (such as SF3B1 and SRSF2) have been identified in myeloid blood diseases such as myelodysplastic syndrome. The study of abnormal RNA splicing in hematological tumors has received extensive attention and has been promoted. Clinical trials of splicing inhibitors for the treatment of hematological tumors. However, similar splicing factor mutations have not been reported in acute lymphoid leukemia.
In order to explore the functional role of RNA aberrant splicing in acute lymphoblastic leukemia, the authors used T-ALL as a research object to screen for splicing-related factors with high expression in T-ALL. It was found that the oncoprotein NOTCH1 directly activates SHQ1 and promotes its abnormally high expression. . SHQ1 is involved in the assembly of RNA-protein complex H/ACA snoRNP, mediates the splicing of U2 snRNA pseudo-uracil, promotes efficient RNA splicing in leukemia cells, and promotes the growth and survival of T-ALL cells and the development of T-ALL. important. The results of RNA deep sequencing showed that SHQ1 inactivation could induce genome-wide splicing efficiency, and the key molecule whose expression level was down-regulated was the oncogene MYC. Overexpression of MYC protein can effectively rescue T-ALL cell death caused by SHQ1 inactivation. The results of this study not only elucidated the important biological functions of SHQ1 in RNA modification, RNA splicing and T cell leukemia, but also revealed a new mechanism of post-transcriptional regulation of oncogene MYC.
The paper is entitled SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival ("SHQ1 regulates RNA splicing to promote the development of T cell leukemia"). The research work was funded by the National Key Research and Development Program and the National Natural Science Foundation.
Solar Camera,Wireless Solar Outdoor Monitoring,Night Vision Solar Camera,Solar Security Camera
Shenzhen Zuomi Technology Co., Ltd. , https://www.zuomicamera.com