Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress.However,the underly...Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress.However,the underlying mechanisms of detained intron(DI)splicing are still largely unknown.Here,we suggest that post-transcriptional DI splicing is paused at the Bact state,an active spliceosome but not catalytically primed,which depends on Smad Nuclear Interacting Protein 1(SNIP1)and RNPS1(a serine-rich RNA binding protein)interaction.RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing.Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA,a basal spliceosomal component.Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration.Therefore,we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing,and that its misregulation contributes to neurodegeneration.展开更多
Yahoo,我最喜欢浏览的网站,Oddly Enough是我最喜欢的专栏之一。这个栏目绝少有中国故事。不料,刚刚开学,就在Yahoo上读到北京大学生在动物园“作孽”的故事。“作孽”者往熊身上泼洒硫酸,后果严重,但他竟然解释:Iwanted to test whethe...Yahoo,我最喜欢浏览的网站,Oddly Enough是我最喜欢的专栏之一。这个栏目绝少有中国故事。不料,刚刚开学,就在Yahoo上读到北京大学生在动物园“作孽”的故事。“作孽”者往熊身上泼洒硫酸,后果严重,但他竟然解释:Iwanted to test whether or not they really are stupid。但是,I wanted to ask whetheror not he really is stupid！】展开更多
基金the Tsinghua-Peking Joint Center for Life Sciences,the Thousand-Talent Young Investigator Program,the IDG/McGovern Institute for Brain Research,the National Natural Science Foundation of China(81371361,92049114,31571097,82101495)The Beijing Municipal Science&Technology Commission(Z181100001518001,Z161100000216154)+1 种基金National Key R&D Program(2017YFC0110205)the Institute for Guo Qiang,Tsinghua University。
文摘Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress.However,the underlying mechanisms of detained intron(DI)splicing are still largely unknown.Here,we suggest that post-transcriptional DI splicing is paused at the Bact state,an active spliceosome but not catalytically primed,which depends on Smad Nuclear Interacting Protein 1(SNIP1)and RNPS1(a serine-rich RNA binding protein)interaction.RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing.Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA,a basal spliceosomal component.Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration.Therefore,we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing,and that its misregulation contributes to neurodegeneration.
文摘Yahoo,我最喜欢浏览的网站,Oddly Enough是我最喜欢的专栏之一。这个栏目绝少有中国故事。不料,刚刚开学,就在Yahoo上读到北京大学生在动物园“作孽”的故事。“作孽”者往熊身上泼洒硫酸,后果严重,但他竟然解释:Iwanted to test whether or not they really are stupid。但是,I wanted to ask whetheror not he really is stupid！】
