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NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development

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Author(s)
Chang-Hyun KimSang-Moo ParkSun-jae LeeYoung-Dae KimSe-Hwan JangSeon-Min WooTaeg-Kyu KwonZee-Yong ParkIk-Joo ChungHye-Ran KimChang-Duk Jun
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Nucleic Acids Res
Issued Date
2021
Volume
49
Issue
10
Abstract
Alternative pre-mRNA splicing is a critical step to generate multiple transcripts, thereby dramatically enlarging the proteomic diversity. Thus, a common feature of most alternative splicing factor knockout models is lethality. However, little is known about lineage-specific alternative splicing regulators in a physiological setting. Here, we report that NSrp70 is selectively expressed in developing thymocytes, highest at the double-positive (DP) stage. Global splicing and transcriptional profiling revealed that NSrp70 regulates the cell cycle and survival of thymocytes by controlling the alternative processing of various RNA splicing factors, including the oncogenic splicing factor SRSF1. A conditional-knockout of Nsrp1 (NSrp70-cKO) using CD4Cre developed severe defects in T cell maturation to single-positive thymocytes, due to insufficient T cell receptor (TCR) signaling and uncontrolled cell growth and death. Mice displayed severe peripheral lymphopenia and could not optimally control tumor growth. This study establishes a model to address the function of lymphoid-lineage-specific alternative splicing factor NSrp70 in a thymic T cell developmental pathway.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Chang-Hyun Kim et al. (2021). NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development. Nucleic Acids Res, 49(10), 5760–5778. doi: 10.1093/nar/gkab389
Type
Article
ISSN
1362-4962
Source
https://academic.oup.com/nar/article/49/10/5760/6284184
DOI
10.1093/nar/gkab389
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43824
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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