整合因子(Integrator)复合体通过调控UsnRNAs(U-rich small nuclear RNAs)的转录成熟过程,影响premRNA的内含子剪切,对生物体内形成成熟mRNA有重要作用。但是在脊椎动物中,整合因子复合体的表达调控及其发育功能研究尚十分缺乏。研究利...整合因子(Integrator)复合体通过调控UsnRNAs(U-rich small nuclear RNAs)的转录成熟过程,影响premRNA的内含子剪切,对生物体内形成成熟mRNA有重要作用。但是在脊椎动物中,整合因子复合体的表达调控及其发育功能研究尚十分缺乏。研究利用斑马鱼(Danio rerio)模型,通过CRISPR/Cas9技术构建了ints12(Integrator subunit 12)的基因敲除品系,得到了2种缺失不同碱基的突变品系。在ints12的合子突变体(Zints12)中,通过荧光定量PCR分析,发现UsnRNA的3′box剪切存在缺陷。与同龄的野生型斑马鱼相比,Zints12体型偏小且表现为全雄。进一步研究发现,在Zints12成体中,细胞增殖相关因子出现显著下调表达,ints12自身pre-mRNA的加工也出现内含子滞留,表明ints12对自身mRNA的剪切存在一个"自循环"式的调控模式。研究获得了斑马鱼的ints12基因敲除纯合突变体并发现ints12通过调控UsnRNA的剪切参与斑马鱼的个体生长和发育。展开更多
Emerging studies support that RNA-binding proteins （RBPs） play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylat...Emerging studies support that RNA-binding proteins （RBPs） play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.展开更多
基金Zhou HuaLin is supported by National Basic Research Program of China(2013CB917803)research fund for the State Key Laboratory of Cog-nitive Neuroscience and Learning from Institute of Biophysics,Chinese Academy of Sciences(7Y1SNY7007)+3 种基金supported by the Ross Maclean Senior Research Fellowship and the Peter Goodenough BequestZhu Li and Liu JiangHong are supported by grants from the Na-tional Major Basic Research Program of China(2010CB529603)the National Natural Science Foundation of China(91132710,31200561)Jane Y.Wu is supported by the US National Institutes of Health
文摘Emerging studies support that RNA-binding proteins （RBPs） play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.
